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The role of caveolin-1 in tumors of the brain - functional and clinical implications

  • Pinar Eser Ocak
  • Umut Ocak
  • Jiping Tang
  • John H. ZhangEmail author
Review
  • 43 Downloads

Abstract

Background

Caveolin-1 (cav-1) is the major structural protein of caveolae, the flask-shaped invaginations of the plasma membrane mainly involved in cell signaling. Today, cav-1 is believed to play a role in a variety of disease processes including cancer, owing to the variations of its expression in association with tumor progression, invasive behavior, metastasis and therapy resistance. Since first detected in the brain, a number of studies has particularly focused on the role of cav-1 in the various steps of brain tumorigenesis. In this review, we discuss the different roles of cav-1 and its contributions to the molecular mechanisms underlying the pathobiology and natural behavior of brain tumors including glial, non-glial and metastatic subtypes. These contributions could be attributed to its co-localization with important players in tumorigenesis within the lipid-enriched domains of the plasma membrane. In that regard, the ability of cav-1 to interact with various cell signaling molecules as well as the impact of caveolae depletion on important pathways acting in brain tumor pathogenesis are noteworthy. We also discuss conversant causes hampering the treatment of malignant glial tumors such as limited transport of chemotherapeutics across the blood tumor barrier and resistance to chemoradiotherapy, by focusing on the molecular fundamentals involving cav-1 participation.

Conclusions

Cav-1 has the potential to pivot the molecular basis underlying the pathobiology of brain tumors, particularly the malignant glial subtype. In addition, the regulatory effect of cav-1-dependent and caveola-mediated transcellular transport on the permeability of the blood tumor barrier could be of benefit to overcome the restricted transport across brain barriers when applying chemotherapeutics. The association of cav-1 with tumors of the brain other than malignant gliomas deserves to be underlined, as well given the evidence suggesting its potential in predicting tumor grade and recurrence rates together with determining patient prognosis in oligodendrogliomas, ependymomas, meningiomas, vestibular schwannomas and brain metastases.

Keywords

Caveolin-1 Brain tumor Blood brain barrier Glioma 

Notes

Authors’ contributions

PEO analyzed the literature, wrote the review and draw the figs. UO structured the sections, designed and substantially contributed to the development of the review. JT and JHZ supervised and critically revised the paper. All authors have read and approved the submitted manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

References

  1. 1.
    A.W. Cohen, R. Hnasko, W. Schubert, M.P. Lisanti, Role of caveolae and caveolins in health and disease. Physiol Rev 84, 1341–1379 (2004)CrossRefPubMedGoogle Scholar
  2. 2.
    F. Galbiati, D. Volonte, J. Liu, F. Capozza, P.G. Frank, L. Zhu, R.G. Pestell, M.P. Lisanti, Caveolin-1 expression negatively regulates cell cycle progression by inducing G(0)/G(1) arrest via a p53/p21(WAF1/Cip1)-dependent mechanism. Mol Biol Cell 12, 2229–2244 (2001)CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    V.A. Torres, J.C. Tapia, D.A. Rodriguez, M. Parraga, P. Lisboa, M. Montoya, L. Leyton, A.F. Quest, Caveolin-1 controls cell proliferation and cell death by suppressing expression of the inhibitor of apoptosis protein survivin. J Cell Sci 119, 1812–1823 (2006)CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    K.S. Song, P.E. Scherer, Z. Tang, T. Okamoto, S. Li, M. Chafel, C. Chu, D.S. Kohtz, M.P. Lisanti, Expression of caveolin-3 in skeletal, cardiac, and smooth muscle cells. Caveolin-3 is a component of the sarcolemma and co-fractionates with dystrophin and dystrophin-associated glycoproteins. J Biol Chem 271, 15160–15165 (1996)CrossRefGoogle Scholar
  5. 5.
    M.M. Hill, M. Bastiani, R. Luetterforst, M. Kirkham, A. Kirkham, S.J. Nixon, P. Walser, D. Abankwa, V.M. Oorschot, S. Martin, J.F. Hancock, R.G. Parton, PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function. Cell 132, 113–124 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    A.J. Koleske, D. Baltimore, M.P. Lisanti, Reduction of caveolin and caveolae in oncogenically transformed cells. Proc Natl Acad Sci U S A 92, 1381–1385 (1995)CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    S.W. Lee, C.L. Reimer, P. Oh, D.B. Campbell, J.E. Schnitzer, Tumor cell growth inhibition by caveolin re-expression in human breast cancer cells. Oncogene 16, 1391–1397 (1998)CrossRefPubMedGoogle Scholar
  8. 8.
    H. Lee, D.S. Park, B. Razani, R.G. Russell, R.G. Pestell, M.P. Lisanti, Caveolin-1 mutations (P132L and null) and the pathogenesis of breast cancer: Caveolin-1 (P132L) behaves in a dominant-negative manner and caveolin-1 (−/−) null mice show mammary epithelial cell hyperplasia. Am J Pathol 161, 1357–1369 (2002)CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Z.D. Nassar, M.M. Hill, R.G. Parton, M.O. Parat, Caveola-forming proteins caveolin-1 and PTRF in prostate cancer. Nat Rev Urol 10, 529–536 (2013)CrossRefPubMedGoogle Scholar
  10. 10.
    C. Schoch, T. Haferlach, S. Bursch, D. Gerstner, S. Schnittger, M. Dugas, W. Kern, H. Loffler, W. Hiddemann, Loss of genetic material is more common than gain in acute myeloid leukemia with complex aberrant karyotype: A detailed analysis of 125 cases using conventional chromosome analysis and fluorescence in situ hybridization including 24-color FISH. Genes Chromosomes Cancer 35, 20–29 (2002)CrossRefPubMedGoogle Scholar
  11. 11.
    L. Cheng, G.T. MacLennan, S. Zhang, M. Wang, M. Zhou, P.H. Tan, S. Foster, A. Lopez-Beltran, R. Montironi, Evidence for polyclonal origin of multifocal clear cell renal cell carcinoma. Clin Cancer Res 14, 8087–8093 (2008)CrossRefPubMedGoogle Scholar
  12. 12.
    J. Xiong, D. Wang, A. Wei, H. Lu, C. Tan, A. Li, J. Tang, Y. Wang, S. He, X. Liu, W. Hu, Deregulated expression of miR-107 inhibits metastasis of PDAC through inhibition PI3K/Akt signaling via caveolin-1 and PTEN. Exp Cell Res 361, 316–323 (2017)CrossRefPubMedGoogle Scholar
  13. 13.
    J. Jankovic, S. Tatic, V. Bozic, V. Zivaljevic, D. Cvejic, S. Paskas, Inverse expression of caveolin-1 and EGFR in thyroid cancer patients. Hum Pathol 61, 164–172 (2017)CrossRefPubMedGoogle Scholar
  14. 14.
    B.K. Ryu, M.G. Lee, N.H. Kim, K.Y. Lee, S.J. Oh, J.R. Moon, H.J. Kim, S.G. Chi, Bidirectional alteration of Cav-1 expression is associated with mitogenic conversion of its function in gastric tumor progression. BMC Cancer 17(766) (2017)Google Scholar
  15. 15.
    C. Aguirre-Portoles, J. Feliu, G. Reglero, A. Ramirez de Molina, ABCA1 overexpression worsens colorectal cancer prognosis by facilitating tumour growth and caveolin-1-dependent invasiveness, and these effects can be ameliorated using the BET inhibitor apabetalone. Mol Oncol 12, 1735-1752 (2018)Google Scholar
  16. 16.
    Y.N. Liang, Y. Liu, L. Wang, G. Yao, X. Li, X. Meng, F. Wang, M. Li, D. Tong, J. Geng, Combined caveolin-1 and epidermal growth factor receptor expression as a prognostic marker for breast cancer. Oncol Lett 15, 9271–9282 (2018)PubMedPubMedCentralGoogle Scholar
  17. 17.
    L. Bazzani, S. Donnini, A. Giachetti, G. Christofori, M. Ziche, PGE2 mediates EGFR internalization and nuclear translocation via caveolin endocytosis promoting its transcriptional activity and proliferation in human NSCLC cells. Oncotarget 9, 14939–14958 (2018)PubMedPubMedCentralGoogle Scholar
  18. 18.
    P.L. Cameron, J.W. Ruffin, R. Bollag, H. Rasmussen, R.S. Cameron, Identification of caveolin and caveolin-related proteins in the brain. J Neurosci 17, 9520–9535 (1997)CrossRefPubMedGoogle Scholar
  19. 19.
    F. Galbiati, D. Volonte, O. Gil, G. Zanazzi, J.L. Salzer, M. Sargiacomo, P.E. Scherer, J.A. Engelman, A. Schlegel, M. Parenti, T. Okamoto, M.P. Lisanti, Expression of caveolin-1 and -2 in differentiating PC12 cells and dorsal root ganglion neurons: Caveolin-2 is up-regulated in response to cell injury. Proc Natl Acad Sci U S A 95, 10257–10262 (1998)CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    T. Ikezu, H. Ueda, B.D. Trapp, K. Nishiyama, J.F. Sha, D. Volonte, F. Galbiati, A.L. Byrd, G. Bassell, H. Serizawa, W.S. Lane, M.P. Lisanti, T. Okamoto, Affinity-purification and characterization of caveolins from the brain: Differential expression of caveolin-1, −2, and −3 in brain endothelial and astroglial cell types. Brain Res 804, 177–192 (1998)CrossRefPubMedGoogle Scholar
  21. 21.
    P.L. Cameron, C. Liu, D.K. Smart, S.T. Hantus, J.R. Fick, R.S. Cameron, Caveolin-1 expression is maintained in rat and human astroglioma cell lines. Glia 37, 275–290 (2002)CrossRefPubMedGoogle Scholar
  22. 22.
    C.D. Stiles, Cancer of the central nervous system. Review of an AACR special conference in cancer research with the joint section on tumors of the AANS/CNS (San Diego, CA, June 7-11, 1997). Biochim Biophys Acta 1377, R1–10 (1998)PubMedGoogle Scholar
  23. 23.
    I.F. Pollack, Pediatric brain tumors. Semin Surg Oncol 16, 73–90 (1999)CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    P. Kleihues, H. Ohgaki, Primary and secondary glioblastomas: From concept to clinical diagnosis. Neuro-Oncology 1, 44–51 (1999)CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    R.S. Faccion, P.S. Bernardo, G.P.F. de Lopes, L.S. Bastos, C.L. Teixeira, J.A. de Oliveira, P.V. Fernandes, L.G. Dubois, L. Chimelli, R.C. Maia, p53 expression and subcellular survivin localization improve the diagnosis and prognosis of patients with diffuse astrocytic tumors. Cell Oncol 41, 141–157 (2018)CrossRefGoogle Scholar
  26. 26.
    M.O. Taskapilioglu, U. Aktas, P. Eser, S. Tolunay, A. Bekar, Multiple extracranial metastases from secondary glioblastoma: A case report and review of the literature. Turk Neurosurg 23, 824-827 (2013)Google Scholar
  27. 27.
    R. Stupp, M.E. Hegi, W.P. Mason, M.J. van den Bent, M.J. Taphoorn, R.C. Janzer, S.K. Ludwin, A. Allgeier, B. Fisher, K. Belanger, P. Hau, A.A. Brandes, J. Gijtenbeek, C. Marosi, C.J. Vecht, K. Mokhtari, P. Wesseling, S. Villa, E. Eisenhauer, T. Gorlia, M. Weller, D. Lacombe, J.G. Cairncross, R.O. Mirimanoff, R. European organisation for, T. treatment of Cancer brain, G. radiation oncology and G. National Cancer Institute of Canada clinical trials, effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10, 459–466 (2009)CrossRefGoogle Scholar
  28. 28.
    R. Stupp, W.P. Mason, M.J. van den Bent, M. Weller, B. Fisher, M.J. Taphoorn, K. Belanger, A.A. Brandes, C. Marosi, U. Bogdahn, J. Curschmann, R.C. Janzer, S.K. Ludwin, T. Gorlia, A. Allgeier, D. Lacombe, J.G. Cairncross, E. Eisenhauer, R.O. Mirimanoff, R. European organisation for, T. treatment of Cancer brain, G. radiotherapy and G. National Cancer Institute of Canada clinical trials, radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352, 987–996 (2005)CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    M.A. Forget, R.R. Desrosiers, M. Del, R. Moumdjian, D. Shedid, F. Berthelet, R. Beliveau, The expression of rho proteins decreases with human brain tumor progression: Potential tumor markers. Clin Exp Metastasis 19, 9–15 (2002)CrossRefPubMedGoogle Scholar
  30. 30.
    A. Abulrob, S. Giuseppin, M.F. Andrade, A. McDermid, M. Moreno, D. Stanimirovic, Interactions of EGFR and caveolin-1 in human glioblastoma cells: Evidence that tyrosine phosphorylation regulates EGFR association with caveolae. Oncogene 23, 6967–6979 (2004)CrossRefPubMedGoogle Scholar
  31. 31.
    V. Barresi, F.R. Buttarelli, E.E. Vitarelli, A. Arcella, M. Antonelli, F. Giangaspero, Caveolin-1 expression in diffuse gliomas: Correlation with the proliferation index, epidermal growth factor receptor, p53, and 1p/19q status. Hum Pathol 40, 1738–1746 (2009)CrossRefPubMedGoogle Scholar
  32. 32.
    P. Kucharzewska, H.C. Christianson, J.E. Welch, K.J. Svensson, E. Fredlund, M. Ringner, M. Morgelin, E. Bourseau-Guilmain, J. Bengzon, M. Belting, Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development. Proc Natl Acad Sci U S A 110, 7312–7317 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    S. Shimato, L.M. Anderson, M. Asslaber, J.N. Bruce, P. Canoll, D.E. Anderson, R.C. Anderson, Inhibition of caveolin-1 restores myeloid cell function in human glioblastoma. PLoS One 8, e77397 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    P. Cassoni, R. Senetta, I. Castellano, E. Ortolan, M. Bosco, I. Magnani, A. Ducati, Caveolin-1 expression is variably displayed in astroglial-derived tumors and absent in oligodendrogliomas: Concrete premises for a new reliable diagnostic marker in gliomas. Am J Surg Pathol 31, 760–769 (2007)CrossRefPubMedGoogle Scholar
  35. 35.
    R. Senetta, E. Trevisan, R. Ruda, E. Maldi, L. Molinaro, F. Lefranc, L. Chiusa, M. Lanotte, R. Soffietti, P. Cassoni, Caveolin 1 expression independently predicts shorter survival in oligodendrogliomas. J Neuropathol Exp Neurol 68, 425–431 (2009)CrossRefPubMedGoogle Scholar
  36. 36.
    R. Senetta, C. Miracco, S. Lanzafame, L. Chiusa, R. Caltabiano, A. Galia, G. Stella, P. Cassoni, Epidermal growth factor receptor and caveolin-1 coexpression identifies adult supratentorial ependymomas with rapid unfavorable outcomes. Neuro-Oncology 13, 176–183 (2011)CrossRefPubMedGoogle Scholar
  37. 37.
    E.C. Cosset, J. Godet, N. Entz-Werle, E. Guerin, D. Guenot, S. Froelich, D. Bonnet, S. Pinel, F. Plenat, P. Chastagner, M. Dontenwill, S. Martin, Involvement of the TGFbeta pathway in the regulation of alpha5 beta1 integrins by caveolin-1 in human glioblastoma. Int J Cancer 131, 601–611 (2012)CrossRefPubMedGoogle Scholar
  38. 38.
    C. Chen, L. Chen, Y. Yao, Z. Qin, H. Chen, Nucleolin overexpression is associated with an unfavorable outcome for ependymoma: A multifactorial analysis of 176 patients. J Neuro-Oncol 127, 43–52 (2016)CrossRefGoogle Scholar
  39. 39.
    P. Duffy, A. Schmandke, A. Schmandke, J. Sigworth, S. Narumiya, W.B. Cafferty, S.M. Strittmatter, Rho-associated kinase II (ROCKII) limits axonal growth after trauma within the adult mouse spinal cord. J Neurosci 29, 15266–15276 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    R. Shinohara, D. Thumkeo, H. Kamijo, N. Kaneko, K. Sawamoto, K. Watanabe, H. Takebayashi, H. Kiyonari, T. Ishizaki, T. Furuyashiki, S. Narumiya, A role for mDia, a rho-regulated actin nucleator, in tangential migration of interneuron precursors. Nat Neurosci 15, 373–380, S371–372 (2012)CrossRefPubMedGoogle Scholar
  41. 41.
    A. Tashiro, A. Minden, R. Yuste, Regulation of dendritic spine morphology by the rho family of small GTPases: Antagonistic roles of Rac and rho. Cereb Cortex 10, 927–938 (2000)CrossRefPubMedGoogle Scholar
  42. 42.
    C.D. Nobes, A. Hall, Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81, 53–62 (1995)CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    G. Fritz, I. Just, B. Kaina, Rho GTPases are over-expressed in human tumors. Int J Cancer 81, 682–687 (1999)CrossRefPubMedGoogle Scholar
  44. 44.
    D. Gingras, F. Gauthier, S. Lamy, R.R. Desrosiers, R. Beliveau, Localization of RhoA GTPase to endothelial caveolae-enriched membrane domains. Biochem Biophys Res Commun 247, 888–893 (1998)CrossRefPubMedGoogle Scholar
  45. 45.
    G.J. Pilkington, The paradox of neoplastic glial cell invasion of the brain and apparent metastatic failure. Anticancer Res 17, 4103–4105 (1997)PubMedGoogle Scholar
  46. 46.
    N.L. Tran, W.S. McDonough, B.A. Savitch, S.P. Fortin, J.A. Winkles, M. Symons, M. Nakada, H.E. Cunliffe, G. Hostetter, D.B. Hoelzinger, J.L. Rennert, J.S. Michaelson, L.C. Burkly, C.A. Lipinski, J.C. Loftus, L. Mariani, M.E. Berens, Increased fibroblast growth factor-inducible 14 expression levels promote glioma cell invasion via Rac1 and nuclear factor-kappaB and correlate with poor patient outcome. Cancer Res 66, 9535–9542 (2006)CrossRefPubMedGoogle Scholar
  47. 47.
    S.P. Fortin Ensign, I.T. Mathews, M.H. Symons, M.E. Berens, N.L. Tran, Implications of rho GTPase signaling in Glioma cell invasion and tumor progression. Front Oncol 3(241) (2013)Google Scholar
  48. 48.
    S. Dauth, T. Grevesse, H. Pantazopoulos, P.H. Campbell, B.M. Maoz, S. Berretta, K.K. Parker, Extracellular matrix protein expression is brain region dependent. J Comp Neurol 524, 1309–1336 (2016)CrossRefPubMedGoogle Scholar
  49. 49.
    U. Gunthert, C. Schwarzler, B. Wittig, J. Laman, P. Ruiz, R. Stauder, A. Bloem, F. Smadja-Joffe, M. Zoller, A. Rolink, Functional involvement of CD44, a family of cell adhesion molecules, in immune responses, tumour progression and haematopoiesis. Adv Exp Med Biol 451, 43–49 (1998)CrossRefPubMedGoogle Scholar
  50. 50.
    K.N. Sugahara, T. Murai, H. Nishinakamura, H. Kawashima, H. Saya, M. Miyasaka, Hyaluronan oligosaccharides induce CD44 cleavage and promote cell migration in CD44-expressing tumor cells. J Biol Chem 278, 32259–32265 (2003)CrossRefPubMedGoogle Scholar
  51. 51.
    Y. Akiyama, S. Jung, B. Salhia, S. Lee, S. Hubbard, M. Taylor, T. Mainprize, K. Akaishi, W. van Furth, J.T. Rutka, Hyaluronate receptors mediating glioma cell migration and proliferation. J Neuro-Oncol 53, 115–127 (2001)CrossRefGoogle Scholar
  52. 52.
    S.M. Ranuncolo, V. Ladeda, S. Specterman, M. Varela, J. Lastiri, A. Morandi, E. Matos, E. Bal de Kier Joffe, L. Puricelli, M.G. Pallotta, CD44 expression in human gliomas. J Surg Oncol 79, 30–35; discussion 35-36 (2002)CrossRefPubMedGoogle Scholar
  53. 53.
    S.K. Singh, I.D. Clarke, M. Terasaki, V.E. Bonn, C. Hawkins, J. Squire, P.B. Dirks, Identification of a cancer stem cell in human brain tumors. Cancer Res 63, 5821–5828 (2003)Google Scholar
  54. 54.
    J.D. Lathia, S.C. Mack, E.E. Mulkearns-Hubert, C.L. Valentim, J.N. Rich, Cancer stem cells in glioblastoma. Genes Dev 29, 1203–1217 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    E.M. Ahmed, G. Bandopadhyay, B. Coyle, A. Grabowska, A HIF-independent, CD133-mediated mechanism of cisplatin resistance in glioblastoma cells. Cell Oncol 41, 319–328 (2018)CrossRefGoogle Scholar
  56. 56.
    I. Okamoto, Y. Kawano, H. Tsuiki, J. Sasaki, M. Nakao, M. Matsumoto, M. Suga, M. Ando, M. Nakajima, H. Saya, CD44 cleavage induced by a membrane-associated metalloprotease plays a critical role in tumor cell migration. Oncogene 18, 1435–1446 (1999)CrossRefPubMedGoogle Scholar
  57. 57.
    M. Kajita, Y. Itoh, T. Chiba, H. Mori, A. Okada, H. Kinoh, M. Seiki, Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. J Cell Biol 153, 893–904 (2001)CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    H. Mori, T. Tomari, N. Koshikawa, M. Kajita, Y. Itoh, H. Sato, H. Tojo, I. Yana, M. Seiki, CD44 directs membrane-type 1 matrix metalloproteinase to lamellipodia by associating with its hemopexin-like domain. EMBO J 21, 3949–3959 (2002)CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    B. Annabi, M. Lachambre, N. Bousquet-Gagnon, M. Page, D. Gingras, R. Beliveau, Localization of membrane-type 1 matrix metalloproteinase in caveolae membrane domains. Biochem J 353, 547–553 (2001)CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    B. Annabi, S. Thibeault, R. Moumdjian, R. Beliveau, Hyaluronan cell surface binding is induced by type I collagen and regulated by caveolae in glioma cells. J Biol Chem 279, 21888–21896 (2004)CrossRefPubMedGoogle Scholar
  61. 61.
    B. Annabi, M. Bouzeghrane, R. Moumdjian, A. Moghrabi, R. Beliveau, Probing the infiltrating character of brain tumors: Inhibition of RhoA/ROK-mediated CD44 cell surface shedding from glioma cells by the green tea catechin EGCg. J Neurochem 94, 906–916 (2005)CrossRefPubMedGoogle Scholar
  62. 62.
    R. Nishikawa, X.D. Ji, R.C. Harmon, C.S. Lazar, G.N. Gill, W.K. Cavenee, H.J. Huang, A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc Natl Acad Sci U S A 91, 7727–7731 (1994)CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    C. Lopez-Gines, L. Navarro, L. Munoz-Hidalgo, E. Buso, J.M. Morales, R. Gil-Benso, M. Gregori-Romero, J. Megias, P. Roldan, R. Segura-Sabater, J.M. Almerich-Silla, D. Monleon, M. Cerda-Nicolas, Association between epidermal growth factor receptor amplification and ADP-ribosylation factor 1 methylation in human glioblastoma. Cell Oncol 40, 389–399 (2017)CrossRefGoogle Scholar
  64. 64.
    B.R. Voldborg, L. Damstrup, M. Spang-Thomsen, H.S. Poulsen, Epidermal growth factor receptor (EGFR) and EGFR mutations, function and possible role in clinical trials. Ann Oncol 8, 1197–1206 (1997)CrossRefPubMedGoogle Scholar
  65. 65.
    M. Nagane, H. Lin, W.K. Cavenee, H.J. Huang, Aberrant receptor signaling in human malignant gliomas: Mechanisms and therapeutic implications. Cancer Lett 162 Suppl, S17–S21 (2001)CrossRefPubMedGoogle Scholar
  66. 66.
    Y. Narita, M. Nagane, K. Mishima, H.J. Huang, F.B. Furnari, W.K. Cavenee, Mutant epidermal growth factor receptor signaling down-regulates p27 through activation of the phosphatidylinositol 3-kinase/Akt pathway in glioblastomas. Cancer Res 62, 6764–6769 (2002)PubMedGoogle Scholar
  67. 67.
    J. Couet, M. Sargiacomo, M.P. Lisanti, Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities. J Biol Chem 272, 30429–30438 (1997)CrossRefPubMedGoogle Scholar
  68. 68.
    C. Mineo, G.N. Gill, R.G. Anderson, Regulated migration of epidermal growth factor receptor from caveolae. J Biol Chem 274, 30636–30643 (1999)CrossRefPubMedGoogle Scholar
  69. 69.
    T.F. Cloughesy, K. Yoshimoto, P. Nghiemphu, K. Brown, J. Dang, S. Zhu, T. Hsueh, Y. Chen, W. Wang, D. Youngkin, L. Liau, N. Martin, D. Becker, M. Bergsneider, A. Lai, R. Green, T. Oglesby, M. Koleto, J. Trent, S. Horvath, P.S. Mischel, I.K. Mellinghoff, C.L. Sawyers, Antitumor activity of rapamycin in a phase I trial for patients with recurrent PTEN-deficient glioblastoma. PLoS Med 5, e8 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    S.F. Hussain, L.Y. Kong, J. Jordan, C. Conrad, T. Madden, I. Fokt, W. Priebe, A.B. Heimberger, A novel small molecule inhibitor of signal transducers and activators of transcription 3 reverses immune tolerance in malignant glioma patients. Cancer Res 67, 9630–9636 (2007)CrossRefPubMedGoogle Scholar
  71. 71.
    A. Iwamaru, S. Szymanski, E. Iwado, H. Aoki, T. Yokoyama, I. Fokt, K. Hess, C. Conrad, T. Madden, R. Sawaya, S. Kondo, W. Priebe, Y. Kondo, A novel inhibitor of the STAT3 pathway induces apoptosis in malignant glioma cells both in vitro and in vivo. Oncogene 26, 2435–2444 (2007)CrossRefPubMedGoogle Scholar
  72. 72.
    H.W. Lo, X. Cao, H. Zhu, F. Ali-Osman, Constitutively activated STAT3 frequently coexpresses with epidermal growth factor receptor in high-grade gliomas and targeting STAT3 sensitizes them to Iressa and alkylators. Clin Cancer Res 14, 6042–6054 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    S.O. Rahaman, P.C. Harbor, O. Chernova, G.H. Barnett, M.A. Vogelbaum, S.J. Haque, Inhibition of constitutively active Stat3 suppresses proliferation and induces apoptosis in glioblastoma multiforme cells. Oncogene 21, 8404–8413 (2002)CrossRefPubMedGoogle Scholar
  74. 74.
    R. Ghildiyal, D. Dixit, E. Sen, EGFR inhibitor BIBU induces apoptosis and defective autophagy in glioma cells. Mol Carcinog 52, 970–982 (2013)CrossRefPubMedGoogle Scholar
  75. 75.
    X.Q. Wang, Q. Yan, P. Sun, J.W. Liu, L. Go, S.M. McDaniel, A.S. Paller, Suppression of epidermal growth factor receptor signaling by protein kinase C-alpha activation requires CD82, caveolin-1, and ganglioside. Cancer Res 67, 9986–9995 (2007)CrossRefPubMedGoogle Scholar
  76. 76.
    M. Jakobisiak, J. Golab, Potential antitumor effects of statins (review). Int J Oncol 23, 1055–1069 (2003)PubMedGoogle Scholar
  77. 77.
    H. Komuro, T. Kumada, Ca2+ transients control CNS neuronal migration. Cell Calcium 37, 387–393 (2005)CrossRefPubMedGoogle Scholar
  78. 78.
    A.K. Weaver, V.C. Bomben, H. Sontheimer, Expression and function of calcium-activated potassium channels in human glioma cells. Glia 54, 223–233 (2006)CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    A. Arcangeli, O. Crociani, E. Lastraioli, A. Masi, S. Pillozzi, A. Becchetti, Targeting ion channels in cancer: A novel frontier in antineoplastic therapy. Curr Med Chem 16, 66–93 (2009)CrossRefPubMedGoogle Scholar
  80. 80.
    H. Komuro, P. Rakic, Orchestration of neuronal migration by activity of ion channels, neurotransmitter receptors, and intracellular Ca2+ fluctuations. J Neurobiol 37, 110–130 (1998)CrossRefPubMedGoogle Scholar
  81. 81.
    A. Bordey, H. Sontheimer, J. Trouslard, Muscarinic activation of BK channels induces membrane oscillations in glioma cells and leads to inhibition of cell migration. J Membr Biol 176, 31–40 (2000)CrossRefPubMedGoogle Scholar
  82. 82.
    A. Fabian, T. Fortmann, P. Dieterich, C. Riethmuller, P. Schon, S. Mally, B. Nilius, A. Schwab, TRPC1 channels regulate directionality of migrating cells. Pflugers Arch 457, 475–484 (2008)CrossRefPubMedGoogle Scholar
  83. 83.
    V.C. Bomben, H. Sontheimer, Disruption of transient receptor potential canonical channel 1 causes incomplete cytokinesis and slows the growth of human malignant gliomas. Glia 58, 1145–1156 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    V.C. Bomben, H.W. Sontheimer, Inhibition of transient receptor potential canonical channels impairs cytokinesis in human malignant gliomas. Cell Prolif 41, 98–121 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    V.C. Bomben, K.L. Turner, T.T. Barclay, H. Sontheimer, Transient receptor potential canonical channels are essential for chemotactic migration of human malignant gliomas. J Cell Physiol 226, 1879–1888 (2011)CrossRefPubMedGoogle Scholar
  86. 86.
    C.V. Remillard, J.X. Yuan, Transient receptor potential channels and caveolin-1: Good friends in tight spaces. Mol Pharmacol 70, 1151–1154 (2006)CrossRefPubMedGoogle Scholar
  87. 87.
    Y. El Hiani, V. Lehen'kyi, H. Ouadid-Ahidouch, A. Ahidouch, Activation of the calcium-sensing receptor by high calcium induced breast cancer cell proliferation and TRPC1 cation channel over-expression potentially through EGFR pathways. Arch Biochem Biophys 486, 58–63 (2009)CrossRefPubMedGoogle Scholar
  88. 88.
    S. Feske, Calcium signalling in lymphocyte activation and disease. Nat Rev Immunol 7, 690–702 (2007)CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    P. Parsons-Wingerter, I.M. Kasman, S. Norberg, A. Magnussen, S. Zanivan, A. Rissone, P. Baluk, C.J. Favre, U. Jeffry, R. Murray, D.M. McDonald, Uniform overexpression and rapid accessibility of alpha5beta1 integrin on blood vessels in tumors. Am J Pathol 167, 193–211 (2005)CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    O. Stoeltzing, W. Liu, N. Reinmuth, F. Fan, G.C. Parry, A.A. Parikh, M.F. McCarty, C.D. Bucana, A.P. Mazar, L.M. Ellis, Inhibition of integrin alpha5beta1 function with a small peptide (ATN-161) plus continuous 5-FU infusion reduces colorectal liver metastases and improves survival in mice. Int J Cancer 104, 496–503 (2003)CrossRefPubMedGoogle Scholar
  91. 91.
    K. Sawada, A.K. Mitra, A.R. Radjabi, V. Bhaskar, E.O. Kistner, M. Tretiakova, S. Jagadeeswaran, A. Montag, A. Becker, H.A. Kenny, M.E. Peter, V. Ramakrishnan, S.D. Yamada, E. Lengyel, Loss of E-cadherin promotes ovarian cancer metastasis via alpha 5-integrin, which is a therapeutic target. Cancer Res 68, 2329–2339 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    A. Maglott, P. Bartik, S. Cosgun, P. Klotz, P. Ronde, G. Fuhrmann, K. Takeda, S. Martin, M. Dontenwill, The small alpha5beta1 integrin antagonist, SJ749, reduces proliferation and clonogenicity of human astrocytoma cells. Cancer Res 66, 6002–6007 (2006)CrossRefPubMedGoogle Scholar
  93. 93.
    M.A. del Pozo, N. Balasubramanian, N.B. Alderson, W.B. Kiosses, A. Grande-Garcia, R.G. Anderson, M.A. Schwartz, Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization. Nat Cell Biol 7, 901–908 (2005)CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    K.K. Wary, A. Mariotti, C. Zurzolo, F.G. Giancotti, A requirement for caveolin-1 and associated kinase Fyn in integrin signaling and anchorage-dependent cell growth. Cell 94, 625–634 (1998)CrossRefPubMedGoogle Scholar
  95. 95.
    K.K. Wary, F. Mainiero, S.J. Isakoff, E.E. Marcantonio, F.G. Giancotti, The adaptor protein Shc couples a class of integrins to the control of cell cycle progression. Cell 87, 733–743 (1996)CrossRefPubMedGoogle Scholar
  96. 96.
    S. Martin, E.C. Cosset, J. Terrand, A. Maglott, K. Takeda, M. Dontenwill, Caveolin-1 regulates glioblastoma aggressiveness through the control of alpha(5)beta(1) integrin expression and modulates glioblastoma responsiveness to SJ749, an alpha(5)beta(1) integrin antagonist. Biochim Biophys Acta 1793, 354–367 (2009)CrossRefPubMedGoogle Scholar
  97. 97.
    A.W. Cohen, D.S. Park, S.E. Woodman, T.M. Williams, M. Chandra, J. Shirani, A. Pereira de Souza, R.N. Kitsis, R.G. Russell, L.M. Weiss, B. Tang, L.A. Jelicks, S.M. Factor, V. Shtutin, H.B. Tanowitz, M.P. Lisanti, Caveolin-1 null mice develop cardiac hypertrophy with hyperactivation of p42/44 MAP kinase in cardiac fibroblasts. Am J Physiol Cell Physiol 284, C457–C474 (2003)CrossRefPubMedGoogle Scholar
  98. 98.
    A. Wesolowska, A. Kwiatkowska, L. Slomnicki, M. Dembinski, A. Master, M. Sliwa, K. Franciszkiewicz, S. Chouaib, B. Kaminska, Microglia-derived TGF-beta as an important regulator of glioblastoma invasion--an inhibition of TGF-beta-dependent effects by shRNA against human TGF-beta type II receptor. Oncogene 27, 918–930 (2008)CrossRefPubMedGoogle Scholar
  99. 99.
    A. Bruna, R.S. Darken, F. Rojo, A. Ocana, S. Penuelas, A. Arias, R. Paris, A. Tortosa, J. Mora, J. Baselga, J. Seoane, High TGFbeta-Smad activity confers poor prognosis in glioma patients and promotes cell proliferation depending on the methylation of the PDGF-B gene. Cancer Cell 11, 147–160 (2007)CrossRefPubMedGoogle Scholar
  100. 100.
    M. Uhl, S. Aulwurm, J. Wischhusen, M. Weiler, J.Y. Ma, R. Almirez, R. Mangadu, Y.W. Liu, M. Platten, U. Herrlinger, A. Murphy, D.H. Wong, W. Wick, L.S. Higgins, M. Weller, SD-208, a novel transforming growth factor beta receptor I kinase inhibitor, inhibits growth and invasiveness and enhances immunogenicity of murine and human glioma cells in vitro and in vivo. Cancer Res 64, 7954–7961 (2004)CrossRefPubMedGoogle Scholar
  101. 101.
    M.D. Hjelmeland, A.B. Hjelmeland, S. Sathornsumetee, E.D. Reese, M.H. Herbstreith, N.J. Laping, H.S. Friedman, D.D. Bigner, X.F. Wang, J.N. Rich, SB-431542, a small molecule transforming growth factor-beta-receptor antagonist, inhibits human glioma cell line proliferation and motility. Mol Cancer Ther 3, 737–745 (2004)PubMedGoogle Scholar
  102. 102.
    S. Kim, G. Buchlis, Z.G. Fridlender, J. Sun, V. Kapoor, G. Cheng, A. Haas, H.K. Cheung, X. Zhang, M. Corbley, L.R. Kaiser, L. Ling, S.M. Albelda, Systemic blockade of transforming growth factor-beta signaling augments the efficacy of immunogene therapy. Cancer Res 68, 10247–10256 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    P. Hau, P. Jachimczak, R. Schlingensiepen, F. Schulmeyer, T. Jauch, A. Steinbrecher, A. Brawanski, M. Proescholdt, J. Schlaier, J. Buchroithner, J. Pichler, G. Wurm, M. Mehdorn, R. Strege, G. Schuierer, V. Villarrubia, F. Fellner, O. Jansen, T. Straube, V. Nohria, M. Goldbrunner, M. Kunst, S. Schmaus, G. Stauder, U. Bogdahn, K.H. Schlingensiepen, Inhibition of TGF-beta2 with AP 12009 in recurrent malignant gliomas: From preclinical to phase I/II studies. Oligonucleotides 17, 201–212 (2007)CrossRefPubMedGoogle Scholar
  104. 104.
    U. Bogdahn, P. Hau, G. Stockhammer, N.K. Venkataramana, A.K. Mahapatra, A. Suri, A. Balasubramaniam, S. Nair, V. Oliushine, V. Parfenov, I. Poverennova, M. Zaaroor, P. Jachimczak, S. Ludwig, S. Schmaus, H. Heinrichs, K.H. Schlingensiepen, G. Trabedersen Glioma Study, Targeted therapy for high-grade glioma with the TGF-beta2 inhibitor trabedersen: Results of a randomized and controlled phase IIb study. Neuro-Oncology 13, 132–142 (2011)CrossRefPubMedGoogle Scholar
  105. 105.
    D.A. Goodenough, J.A. Goliger, D.L. Paul, Connexins, connexons, and intercellular communication. Annu Rev Biochem 65, 475–502 (1996)CrossRefPubMedGoogle Scholar
  106. 106.
    P. Pu, Z. Xia, S. Yu, Q. Huang, Altered expression of Cx43 in astrocytic tumors. Clin Neurol Neurosurg 107, 49–54 (2004)CrossRefPubMedGoogle Scholar
  107. 107.
    L. Soroceanu, T.J. Manning Jr., H. Sontheimer, Reduced expression of connexin-43 and functional gap junction coupling in human gliomas. Glia 33, 107–117 (2001)CrossRefPubMedGoogle Scholar
  108. 108.
    W. Zhang, C. Nwagwu, D.M. Le, V.W. Yong, H. Song, W.T. Couldwell, Increased invasive capacity of connexin43-overexpressing malignant glioma cells. J Neurosurg 99, 1039–1046 (2003)CrossRefPubMedGoogle Scholar
  109. 109.
    J.H. Lin, T. Takano, M.L. Cotrina, G. Arcuino, J. Kang, S. Liu, Q. Gao, L. Jiang, F. Li, H. Lichtenberg-Frate, S. Haubrich, K. Willecke, S.A. Goldman, M. Nedergaard, Connexin 43 enhances the adhesivity and mediates the invasion of malignant glioma cells. J Neurosci 22, 4302–4311 (2002)CrossRefPubMedGoogle Scholar
  110. 110.
    P.R. Gielen, Q. Aftab, N. Ma, V.C. Chen, X. Hong, S. Lozinsky, C.C. Naus, W.C. Sin, Connexin43 confers Temozolomide resistance in human glioma cells by modulating the mitochondrial apoptosis pathway. Neuropharmacology 75, 539–548 (2013)CrossRefPubMedGoogle Scholar
  111. 111.
    S.F. Murphy, R.T. Varghese, S. Lamouille, S. Guo, K.J. Pridham, P. Kanabur, A.M. Osimani, S. Sharma, J. Jourdan, C.M. Rodgers, G.R. Simonds, R.G. Gourdie, Z. Sheng, Connexin 43 inhibition sensitizes Chemoresistant glioblastoma cells to Temozolomide. Cancer Res 76, 139–149 (2016)CrossRefPubMedGoogle Scholar
  112. 112.
    P.O. Strale, J. Clarhaut, C. Lamiche, L. Cronier, M. Mesnil, N. Defamie, Down-regulation of Connexin43 expression reveals the involvement of caveolin-1 containing lipid rafts in human U251 glioblastoma cell invasion. Mol Carcinog 51, 845–860 (2012)CrossRefPubMedGoogle Scholar
  113. 113.
    D.W. Laird, The gap junction proteome and its relationship to disease. Trends Cell Biol 20, 92–101 (2010)CrossRefPubMedGoogle Scholar
  114. 114.
    M. Mesnil, S. Crespin, J.L. Avanzo, M.L. Zaidan-Dagli, Defective gap junctional intercellular communication in the carcinogenic process. Biochim Biophys Acta 1719, 125–145 (2005)CrossRefPubMedGoogle Scholar
  115. 115.
    D.J. Fitzgerald, M. Mesnil, M. Oyamada, H. Tsuda, N. Ito, H. Yamasaki, Changes in gap junction protein (connexin 32) gene expression during rat liver carcinogenesis. J Cell Biochem 41, 97–102 (1989)CrossRefPubMedGoogle Scholar
  116. 116.
    R. Du, K.V. Lu, C. Petritsch, P. Liu, R. Ganss, E. Passegue, H. Song, S. Vandenberg, R.S. Johnson, Z. Werb, G. Bergers, HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell 13, 206–220 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  117. 117.
    B. Raychaudhuri, P. Rayman, J. Ireland, J. Ko, B. Rini, E.C. Borden, J. Garcia, M.A. Vogelbaum, J. Finke, Myeloid-derived suppressor cell accumulation and function in patients with newly diagnosed glioblastoma. Neuro-Oncology 13, 591–599 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    S.F. Hussain, D. Yang, D. Suki, K. Aldape, E. Grimm, A.B. Heimberger, The role of human glioma-infiltrating microglia/macrophages in mediating antitumor immune responses. Neuro-Oncology 8, 261–279 (2006)CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    H. Zhai, F.L. Heppner, S.E. Tsirka, Microglia/macrophages promote glioma progression. Glia 59, 472–485 (2011)CrossRefPubMedGoogle Scholar
  120. 120.
    L.M. Nusblat, M.J. Carroll, C.M. Roth, Crosstalk between M2 macrophages and glioma stem cells. Cell Oncol 40, 471–482 (2017)CrossRefGoogle Scholar
  121. 121.
    R.A. Morgan, L.A. Johnson, J.L. Davis, Z. Zheng, K.D. Woolard, E.A. Reap, S.A. Feldman, N. Chinnasamy, C.T. Kuan, H. Song, W. Zhang, H.A. Fine, S.A. Rosenberg, Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma. Hum Gene Ther 23, 1043–1053 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
  122. 122.
    H. Gao, I.Y. Zhang, L. Zhang, Y. Song, S. Liu, H. Ren, H. Liu, H. Zhou, Y. Su, Y. Yang, B. Badie, S100B suppression alters polarization of infiltrating myeloid-derived cells in gliomas and inhibits tumor growth. Cancer Lett (2018)Google Scholar
  123. 123.
    J. Harris, D. Werling, M. Koss, P. Monaghan, G. Taylor, C.J. Howard, Expression of caveolin by bovine lymphocytes and antigen-presenting cells. Immunology 105, 190–195 (2002)CrossRefPubMedPubMedCentralGoogle Scholar
  124. 124.
    R.A. Santizo, H.L. Xu, E. Galea, S. Muyskens, V.L. Baughman, D.A. Pelligrino, Combined endothelial nitric oxide synthase upregulation and caveolin-1 downregulation decrease leukocyte adhesion in pial venules of ovariectomized female rats. Stroke 33, 613–616 (2002)CrossRefPubMedGoogle Scholar
  125. 125.
    M. Ryuto, M. Ono, H. Izumi, S. Yoshida, H.A. Weich, K. Kohno, M. Kuwano, Induction of vascular endothelial growth factor by tumor necrosis factor alpha in human glioma cells. Possible roles of SP-1. J Biol Chem 271, 28220–28228 (1996)CrossRefPubMedGoogle Scholar
  126. 126.
    M. Tsujimoto, Y.K. Yip, J. Vilcek, Tumor necrosis factor: Specific binding and internalization in sensitive and resistant cells. Proc Natl Acad Sci U S A 82, 7626–7630 (1985)CrossRefPubMedPubMedCentralGoogle Scholar
  127. 127.
    A.A. Beg, D. Baltimore, An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science 274, 782–784 (1996)CrossRefGoogle Scholar
  128. 128.
    D.J. Van Antwerp, S.J. Martin, T. Kafri, D.R. Green, I.M. Verma, Suppression of TNF-alpha-induced apoptosis by NF-kappaB. Science 274, 787–789 (1996)CrossRefPubMedGoogle Scholar
  129. 129.
    Y. Ding, J. Shen, G. Zhang, X. Chen, J. Wu, W. Chen, CD40 controls CXCR5-induced recruitment of myeloid-derived suppressor cells to gastric cancer. Oncotarget 6, 38901–38911 (2015)PubMedPubMedCentralGoogle Scholar
  130. 130.
    S.M. Mangsbo, S. Broos, E. Fletcher, N. Veitonmaki, C. Furebring, E. Dahlen, P. Norlen, M. Lindstedt, T.H. Totterman, P. Ellmark, The human agonistic CD40 antibody ADC-1013 eradicates bladder tumors and generates T-cell-dependent tumor immunity. Clin Cancer Res 21, 1115–1126 (2015)CrossRefPubMedGoogle Scholar
  131. 131.
    M. Chonan, R. Saito, T. Shoji, I. Shibahara, M. Kanamori, Y. Sonoda, M. Watanabe, T. Kikuchi, N. Ishii, T. Tominaga, CD40/CD40L expression correlates with the survival of patients with glioblastomas and an augmentation in CD40 signaling enhances the efficacy of vaccinations against glioma models. Neuro-Oncology 17, 1453–1462 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  132. 132.
    L.V. Pham, A.T. Tamayo, L.C. Yoshimura, P. Lo, N. Terry, P.S. Reid, R.J. Ford, A CD40 signalosome anchored in lipid rafts leads to constitutive activation of NF-kappaB and autonomous cell growth in B cell lymphomas. Immunity 16, 37–50 (2002)CrossRefPubMedGoogle Scholar
  133. 133.
    R. Tewari, S.R. Choudhury, V.S. Mehta, E. Sen, TNFalpha regulates the localization of CD40 in lipid rafts of glioma cells. Mol Biol Rep 39, 8695–8699 (2012)CrossRefPubMedGoogle Scholar
  134. 134.
    H. Li, E.P. Nord, Functional caveolae are a prerequisite for CD40 signaling in human renal proximal tubule cells. Am J Physiol Renal Physiol 286, F711–F719 (2004)CrossRefPubMedGoogle Scholar
  135. 135.
    A.L. Harris, Hypoxia--a key regulatory factor in tumour growth. Nat Rev Cancer 2, 38–47 (2002)CrossRefGoogle Scholar
  136. 136.
    J. Pouyssegur, F. Dayan, N.M. Mazure, Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature 441, 437–443 (2006)CrossRefPubMedPubMedCentralGoogle Scholar
  137. 137.
    J.A. Bertout, S.A. Patel, M.C. Simon, The impact of O2 availability on human cancer. Nat Rev Cancer 8, 967–975 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  138. 138.
    B. Kaur, F.W. Khwaja, E.A. Severson, S.L. Matheny, D.J. Brat, E.G. Van Meir, Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis. Neuro-Oncology 7, 134–153 (2005)CrossRefPubMedPubMedCentralGoogle Scholar
  139. 139.
    W.R. Wilson, M.P. Hay, Targeting hypoxia in cancer therapy. Nat Rev Cancer 11, 393–410 (2011)CrossRefGoogle Scholar
  140. 140.
    N. Ferrara, R.S. Kerbel, Angiogenesis as a therapeutic target. Nature 438, 967–974 (2005)CrossRefPubMedPubMedCentralGoogle Scholar
  141. 141.
    J. Feng, Y. Zhang, X. She, Y. Sun, L. Fan, X. Ren, H. Fu, C. Liu, P. Li, C. Zhao, Q. Liu, Q. Liu, G. Li, M. Wu, Hypermethylated gene ANKDD1A is a candidate tumor suppressor that interacts with FIH1 and decreases HIF1alpha stability to inhibit cell autophagy in the glioblastoma multiforme hypoxia microenvironment. Oncogene 38, 103-119 (2019)Google Scholar
  142. 142.
    J. Skog, T. Wurdinger, S. van Rijn, D.H. Meijer, L. Gainche, M. Sena-Esteves, W.T. Curry Jr., B.S. Carter, A.M. Krichevsky, X.O. Breakefield, Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10, 1470–1476 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  143. 143.
    F. Lan, Q. Qing, Q. Pan, M. Hu, H. Yu, X. Yue, Serum exosomal miR-301a as a potential diagnostic and prognostic biomarker for human glioma. Cell Oncol 41, 25–33 (2018)CrossRefGoogle Scholar
  144. 144.
    H. Valadi, K. Ekstrom, A. Bossios, M. Sjostrand, J.J. Lee, J.O. Lotvall, Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9, 654–659 (2007)CrossRefGoogle Scholar
  145. 145.
    H.W. King, M.Z. Michael, J.M. Gleadle, Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer 12, 421 (2012)Google Scholar
  146. 146.
    A. Kuett, C. Rieger, D. Perathoner, T. Herold, M. Wagner, S. Sironi, K. Sotlar, H.P. Horny, C. Deniffel, H. Drolle, M. Fiegl, IL-8 as mediator in the microenvironment-leukaemia network in acute myeloid leukaemia. Sci Rep 5, 18411 (2015)Google Scholar
  147. 147.
    A.K. Kozlowska, H.C. Tseng, K. Kaur, P. Topchyan, A. Inagaki, V.T. Bui, N. Kasahara, N. Cacalano, A. Jewett, Resistance to cytotoxicity and sustained release of interleukin-6 and interleukin-8 in the presence of decreased interferon-gamma after differentiation of glioblastoma by human natural killer cells. Cancer Immunol Immunother 65, 1085–1097 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  148. 148.
    D.J. Brat, A.C. Bellail, E.G. Van Meir, The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. Neuro-Oncology 7, 122–133 (2005)CrossRefPubMedPubMedCentralGoogle Scholar
  149. 149.
    Y. Wang, O. Roche, C. Xu, E.H. Moriyama, P. Heir, J. Chung, F.C. Roos, Y. Chen, G. Finak, M. Milosevic, B.C. Wilson, B.T. Teh, M. Park, M.S. Irwin, M. Ohh, Hypoxia promotes ligand-independent EGF receptor signaling via hypoxia-inducible factor-mediated upregulation of caveolin-1. Proc Natl Acad Sci U S A 109, 4892–4897 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
  150. 150.
    M. Logozzi, A. De Milito, L. Lugini, M. Borghi, L. Calabro, M. Spada, M. Perdicchio, M.L. Marino, C. Federici, E. Iessi, D. Brambilla, G. Venturi, F. Lozupone, M. Santinami, V. Huber, M. Maio, L. Rivoltini, S. Fais, High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients. PLoS One 4, e5219 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  151. 151.
    F. Wei, C. Ma, T. Zhou, X. Dong, Q. Luo, L. Geng, L. Ding, Y. Zhang, L. Zhang, N. Li, Y. Li, Y. Liu, Exosomes derived from gemcitabine-resistant cells transfer malignant phenotypic traits via delivery of miRNA-222-3p. Mol Cancer 16, 132 (2017)Google Scholar
  152. 152.
    P. Wesseling, M. van den Bent, A. Perry, Oligodendroglioma: Pathology, molecular mechanisms and markers. Acta Neuropathol 129, 809–827 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  153. 153.
    M.J. van den Bent, A.A. Brandes, M.J. Taphoorn, J.M. Kros, M.C. Kouwenhoven, J.Y. Delattre, H.J. Bernsen, M. Frenay, C.C. Tijssen, W. Grisold, L. Sipos, R.H. Enting, P.J. French, W.N. Dinjens, C.J. Vecht, A. Allgeier, D. Lacombe, T. Gorlia, K. Hoang-Xuan, Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: Long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol 31, 344–350 (2013)CrossRefPubMedGoogle Scholar
  154. 154.
    G. Cairncross, M. Wang, E. Shaw, R. Jenkins, D. Brachman, J. Buckner, K. Fink, L. Souhami, N. Laperriere, W. Curran, M. Mehta, Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: Long-term results of RTOG 9402. J Clin Oncol 31, 337–343 (2013)CrossRefPubMedGoogle Scholar
  155. 155.
    M. Kujas, J. Lejeune, A. Benouaich-Amiel, E. Criniere, F. Laigle-Donadey, Y. Marie, K. Mokhtari, M. Polivka, M. Bernier, F. Chretien, A. Couvelard, L. Capelle, H. Duffau, P. Cornu, P. Broet, J. Thillet, A.F. Carpentier, M. Sanson, K. Hoang-Xuan, J.Y. Delattre, Chromosome 1p loss: A favorable prognostic factor in low-grade gliomas. Ann Neurol 58, 322–326 (2005)CrossRefPubMedGoogle Scholar
  156. 156.
    L. Mariani, G. Deiana, E. Vassella, A.R. Fathi, C. Murtin, M. Arnold, I. Vajtai, J. Weis, P. Siegenthaler, M. Schobesberger, M.M. Reinert, Loss of heterozygosity 1p36 and 19q13 is a prognostic factor for overall survival in patients with diffuse WHO grade 2 gliomas treated without chemotherapy. J Clin Oncol 24, 4758–4763 (2006)CrossRefPubMedGoogle Scholar
  157. 157.
    D.N. Louis and International Agency for Research on Cancer, WHO classification of tumours of the central nervous system, Revised 4th edition. Edn. (international agency for research on Cancer, Lyon, 2016)Google Scholar
  158. 158.
    T.S. Armstrong, E. Vera-Bolanos, B.N. Bekele, K. Aldape, M.R. Gilbert, Adult ependymal tumors: Prognosis and the M. D. Anderson Cancer center experience. Neuro-Oncology 12, 862–870 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  159. 159.
    J.L. Villano, C.K. Parker, T.A. Dolecek, Descriptive epidemiology of ependymal tumours in the United States. Br J Cancer 108, 2367–2371 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  160. 160.
    E. Vera-Bolanos, K. Aldape, Y. Yuan, J. Wu, K. Wani, M.J. Necesito-Reyes, H. Colman, G. Dhall, F.S. Lieberman, P. Metellus, T. Mikkelsen, A. Omuro, S. Partap, M. Prados, H.I. Robins, R. Soffietti, J. Wu, M.R. Gilbert, T.S. Armstrong, C. Foundation, Clinical course and progression-free survival of adult intracranial and spinal ependymoma patients. Neuro-Oncology 17, 440–447 (2015)CrossRefPubMedGoogle Scholar
  161. 161.
    F. Mendrzyk, A. Korshunov, A. Benner, G. Toedt, S. Pfister, B. Radlwimmer, P. Lichter, Identification of gains on 1q and epidermal growth factor receptor overexpression as independent prognostic markers in intracranial ependymoma. Clin Cancer Res 12, 2070–2079 (2006)CrossRefPubMedGoogle Scholar
  162. 162.
    R. Ferraldeschi, A. Latif, R.B. Clarke, K. Spence, G. Ashton, J. O'Sullivan, D.G. Evans, A. Howell, W.G. Newman, Lack of caveolin-1 (P132L) somatic mutations in breast cancer. Breast Cancer Res Treat 132, 1185–1186 (2012)CrossRefPubMedGoogle Scholar
  163. 163.
    S. Koike, Y. Kodera, A. Nakao, H. Iwata, Y. Yatabe, Absence of the caveolin-1 P132L mutation in cancers of the breast and other organs. J Mol Diagn 12, 712–717 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  164. 164.
    G. Bonuccelli, M.C. Casimiro, F. Sotgia, C. Wang, M. Liu, S. Katiyar, J. Zhou, E. Dew, F. Capozza, K.M. Daumer, C. Minetti, J.N. Milliman, F. Alpy, M.C. Rio, C. Tomasetto, I. Mercier, N. Flomenberg, P.G. Frank, R.G. Pestell, M.P. Lisanti, Caveolin-1 (P132L), a common breast cancer mutation, confers mammary cell invasiveness and defines a novel stem cell/metastasis-associated gene signature. Am J Pathol 174, 1650–1662 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  165. 165.
    J.N. Sarkaria, G.J. Kitange, C.D. James, R. Plummer, H. Calvert, M. Weller, W. Wick, Mechanisms of chemoresistance to alkylating agents in malignant glioma. Clin Cancer Res 14, 2900–2908 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  166. 166.
    D. Matias, J. Balca-Silva, L.G. Dubois, B. Pontes, V.P. Ferrer, L. Rosario, A. do Carmo, J. Echevarria-Lima, A.B. Sarmento-Ribeiro, M.C. Lopes, V. Moura-Neto, Dual treatment with shikonin and temozolomide reduces glioblastoma tumor growth, migration and glial-to-mesenchymal transition. Cell Oncol 40, 247–261 (2017)CrossRefGoogle Scholar
  167. 167.
    K.E. Warren, Beyond the blood:Brain barrier: The importance of central nervous system (CNS) pharmacokinetics for the treatment of CNS tumors, including diffuse intrinsic pontine Glioma. Front Oncol 8, 239 (2018)Google Scholar
  168. 168.
    N.J. Abbott, A.A. Patabendige, D.E. Dolman, S.R. Yusof, D.J. Begley, Structure and function of the blood-brain barrier. Neurobiol Dis 37, 13–25 (2010)CrossRefPubMedGoogle Scholar
  169. 169.
    D. Knowland, A. Arac, K.J. Sekiguchi, M. Hsu, S.E. Lutz, J. Perrino, G.K. Steinberg, B.A. Barres, A. Nimmerjahn, D. Agalliu, Stepwise recruitment of transcellular and paracellular pathways underlies blood-brain barrier breakdown in stroke. Neuron 82, 603–617 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  170. 170.
    J.A. Siegenthaler, F. Sohet, R. Daneman, Sealing off the CNS': Cellular and molecular regulation of blood-brain barriergenesis. Curr Opin Neurobiol 23, 1057–1064 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  171. 171.
    A. Idbaih, F. Ducray, M. Sierra Del Rio, K. Hoang-Xuan, J.Y. Delattre, Therapeutic application of noncytotoxic molecular targeted therapy in gliomas: Growth factor receptors and angiogenesis inhibitors. Oncologist 13, 978–992 (2008)CrossRefPubMedGoogle Scholar
  172. 172.
    V. Laquintana, A. Trapani, N. Denora, F. Wang, J.M. Gallo, G. Trapani, New strategies to deliver anticancer drugs to brain tumors. Expert Opin Drug Deliv 6, 1017–1032 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  173. 173.
    A. Armulik, G. Genove, M. Mae, M.H. Nisancioglu, E. Wallgard, C. Niaudet, L. He, J. Norlin, P. Lindblom, K. Strittmatter, B.R. Johansson, C. Betsholtz, Pericytes regulate the blood-brain barrier. Nature 468, 557–561 (2010)CrossRefPubMedGoogle Scholar
  174. 174.
    A. Ben-Zvi, B. Lacoste, E. Kur, B.J. Andreone, Y. Mayshar, H. Yan, C. Gu, Mfsd2a is critical for the formation and function of the blood-brain barrier. Nature 509, 507–511 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  175. 175.
    P. Eser Ocak, U. Ocak, P. Sherchan, J.H. Zhang, J. Tang, Insights into major facilitator superfamily domain-containing protein-2a (Mfsd2a) in physiology and pathophysiology. What do we know so far? J Neurosci Res (2018).  https://doi.org/10.1002/jnr.24327
  176. 176.
    N. McDannold, N. Vykhodtseva, K. Hynynen, Targeted disruption of the blood-brain barrier with focused ultrasound: Association with cavitation activity. Phys Med Biol 51, 793–807 (2006)CrossRefPubMedGoogle Scholar
  177. 177.
    K. Hynynen, N. McDannold, N. Vykhodtseva, S. Raymond, R. Weissleder, F.A. Jolesz, N. Sheikov, Focal disruption of the blood-brain barrier due to 260-kHz ultrasound bursts: A method for molecular imaging and targeted drug delivery. J Neurosurg 105, 445–454 (2006)CrossRefPubMedGoogle Scholar
  178. 178.
    C.Y. Xia, Y.H. Liu, P. Wang, Y.X. Xue, Low-frequency ultrasound irradiation increases blood-tumor barrier permeability by transcellular pathway in a rat glioma model. J Mol Neurosci 48, 281–290 (2012)CrossRefPubMedGoogle Scholar
  179. 179.
    T. Aoki, R. Nomura, T. Fujimoto, Tyrosine phosphorylation of caveolin-1 in the endothelium. Exp Cell Res 253, 629–636 (1999)CrossRefPubMedGoogle Scholar
  180. 180.
    T. Inamura, K.L. Black, Bradykinin selectively opens blood-tumor barrier in experimental brain tumors. J Cereb Blood Flow Metab 14, 862–870 (1994)CrossRefPubMedGoogle Scholar
  181. 181.
    L.B. Liu, Y.X. Xue, Y.H. Liu, Bradykinin increases the permeability of the blood-tumor barrier by the caveolae-mediated transcellular pathway. J Neuro-Oncol 99, 187–194 (2010)CrossRefGoogle Scholar
  182. 182.
    L.B. Liu, Y.X. Xue, Y.H. Liu, Y.B. Wang, Bradykinin increases blood-tumor barrier permeability by down-regulating the expression levels of ZO-1, occludin, and claudin-5 and rearranging actin cytoskeleton. J Neurosci Res 86, 1153–1168 (2008)CrossRefPubMedGoogle Scholar
  183. 183.
    C.Y. Xia, Z. Zhang, Y.X. Xue, P. Wang, Y.H. Liu, Mechanisms of the increase in the permeability of the blood-tumor barrier obtained by combining low-frequency ultrasound irradiation with small-dose bradykinin. J Neuro-Oncol 94, 41–50 (2009)CrossRefGoogle Scholar
  184. 184.
    Y.T. Gu, Y.X. Xue, H. Zhang, Y. Li, X.Y. Liang, Adenosine 5′-triphosphate-sensitive potassium channel activator induces the up-regulation of caveolin-1 expression in a rat brain tumor model. Cell Mol Neurobiol 31, 629–634 (2011)CrossRefPubMedGoogle Scholar
  185. 185.
    N.S. Ningaraj, U.T. Sankpal, D. Khaitan, E.A. Meister, T. Vats, Activation of KATP channels increases anticancer drug delivery to brain tumors and survival. Eur J Pharmacol 602, 188–193 (2009)CrossRefPubMedGoogle Scholar
  186. 186.
    A.P. van den Heuvel, A. Schulze, B.M. Burgering, Direct control of caveolin-1 expression by FOXO transcription factors. Biochem J 385, 795–802 (2005)CrossRefPubMedPubMedCentralGoogle Scholar
  187. 187.
    R.P. Cai, Y.X. Xue, J. Huang, J.H. Wang, J.H. Wang, S.Y. Zhao, T.T. Guan, Z. Zhang, Y.T. Gu, NS1619 regulates the expression of caveolin-1 protein in a time-dependent manner via ROS/PI3K/PKB/FoxO1 signaling pathway in brain tumor microvascular endothelial cells. J Neurol Sci 369, 109–118 (2016)CrossRefPubMedGoogle Scholar
  188. 188.
    T.A. Rege, C.Y. Fears, C.L. Gladson, Endogenous inhibitors of angiogenesis in malignant gliomas: nature's antiangiogenic therapy. Neuro-Oncology 7, 106–121 (2005)CrossRefPubMedPubMedCentralGoogle Scholar
  189. 189.
    M.R. Gilbert, J.J. Dignam, T.S. Armstrong, J.S. Wefel, D.T. Blumenthal, M.A. Vogelbaum, H. Colman, A. Chakravarti, S. Pugh, M. Won, R. Jeraj, P.D. Brown, K.A. Jaeckle, D. Schiff, V.W. Stieber, D.G. Brachman, M. Werner-Wasik, I.W. Tremont-Lukats, E.P. Sulman, K.D. Aldape, W.J. Curran Jr., M.P. Mehta, A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370, 699–708 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  190. 190.
    O.L. Chinot, W. Wick, W. Mason, R. Henriksson, F. Saran, R. Nishikawa, A.F. Carpentier, K. Hoang-Xuan, P. Kavan, D. Cernea, A.A. Brandes, M. Hilton, L. Abrey, T. Cloughesy, Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 370, 709–722 (2014)CrossRefPubMedGoogle Scholar
  191. 191.
    L.N. Zhao, Z.H. Yang, Y.H. Liu, H.Q. Ying, H. Zhang, Y.X. Xue, Vascular endothelial growth factor increases permeability of the blood-tumor barrier via caveolae-mediated transcellular pathway. J Mol Neurosci 44, 122–129 (2011)CrossRefPubMedGoogle Scholar
  192. 192.
    Z.H. Yang, L.B. Liu, L.N. Zhao, Y.H. Liu, Y.X. Xue, Permeability of the blood-tumor barrier is enhanced by combining vascular endothelial growth factor with papaverine. J Neurosci Res 92, 703–713 (2014)CrossRefPubMedGoogle Scholar
  193. 193.
    A.C. Berger, H.R. Alexander, G. Tang, P.S. Wu, S.M. Hewitt, E. Turner, E. Kruger, W.D. Figg, A. Grove, E. Kohn, D. Stern, S.K. Libutti, Endothelial monocyte activating polypeptide II induces endothelial cell apoptosis and may inhibit tumor angiogenesis. Microvasc Res 60, 70–80 (2000)CrossRefPubMedGoogle Scholar
  194. 194.
    Z. Li, Y.H. Liu, Y.X. Xue, L.B. Liu, P. Wang, Low-dose endothelial monocyte-activating polypeptide-ii increases permeability of blood-tumor barrier by caveolae-mediated transcellular pathway. J Mol Neurosci 52, 313–322 (2014)CrossRefPubMedGoogle Scholar
  195. 195.
    H. Xie, Y.X. Xue, L.B. Liu, Y.H. Liu, Endothelial-monocyte-activating polypeptide II increases blood-tumor barrier permeability by down-regulating the expression levels of tight junction associated proteins. Brain Res 1319, 13–20 (2010)CrossRefPubMedGoogle Scholar
  196. 196.
    L. Chen, Y. Xue, J. Zheng, X. Liu, J. Liu, J. Chen, Z. Li, Z. Xi, H. Teng, P. Wang, L. Liu, Y. Liu, MiR-429 regulated by endothelial monocyte activating polypeptide-II (EMAP-II) influences blood-tumor barrier permeability by inhibiting the expressions of ZO-1, Occludin and Claudin-5. Front Mol Neurosci 11(35) (2018)Google Scholar
  197. 197.
    Y. Lin, P. Wang, Y.H. Liu, X.L. Shang, L.Y. Chen, Y.X. Xue, DT(270-326) , a truncated diphtheria toxin, increases blood-tumor barrier permeability by upregulating the expression of Caveolin-1. CNS Neurosci Ther 22, 477–487 (2016)CrossRefPubMedGoogle Scholar
  198. 198.
    N.R. Parker, N. Correia, B. Crossley, M.E. Buckland, V.M. Howell, H.R. Wheeler, Correlation of MicroRNA 132 up-regulation with an unfavorable clinical outcome in patients with primary glioblastoma Multiforme treated with radiotherapy plus concomitant and adjuvant Temozolomide chemotherapy. Transl Oncol 6, 742–748 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  199. 199.
    N. Stojcheva, G. Schechtmann, S. Sass, P. Roth, A.M. Florea, A. Stefanski, K. Stuhler, M. Wolter, N.S. Muller, F.J. Theis, M. Weller, G. Reifenberger, C. Happold, MicroRNA-138 promotes acquired alkylator resistance in glioblastoma by targeting the Bcl-2-interacting mediator BIM. Oncotarget 7, 12937–12950 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  200. 200.
    G.S. Markopoulos, E. Roupakia, M. Tokamani, E. Chavdoula, M. Hatziapostolou, C. Polytarchou, K.B. Marcu, A.G. Papavassiliou, R. Sandaltzopoulos, E. Kolettas, A step-by-step microRNA guide to cancer development and metastasis. Cell Oncol 40, 303–339 (2017)CrossRefGoogle Scholar
  201. 201.
    Y. Gu, R. Cai, C. Zhang, Y. Xue, Y. Pan, J. Wang, Z. Zhang, miR-132-3p boosts caveolae-mediated transcellular transport in glioma endothelial cells by targeting PTEN/PI3K/PKB/Src/Cav-1 signaling pathway. FASEB J 33, 441-454 (2019)Google Scholar
  202. 202.
    Y. Li, L.B. Liu, T. Ma, P. Wang, Y.X. Xue, Effect of caveolin-1 on the expression of tight junction-associated proteins in rat glioma-derived microvascular endothelial cells. Int J Clin Exp Pathol 8, 13067–13074 (2015)PubMedPubMedCentralGoogle Scholar
  203. 203.
    N. Strazielle, J.F. Ghersi-Egea, Potential pathways for CNS drug delivery across the blood-cerebrospinal fluid barrier. Curr Pharm Des 22, 5463–5476 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  204. 204.
    S. Yip, J. Miao, D.P. Cahill, A.J. Iafrate, K. Aldape, C.L. Nutt, D.N. Louis, MSH6 mutations arise in glioblastomas during temozolomide therapy and mediate temozolomide resistance. Clin Cancer Res 15, 4622–4629 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  205. 205.
    K. Ujifuku, N. Mitsutake, S. Takakura, M. Matsuse, V. Saenko, K. Suzuki, K. Hayashi, T. Matsuo, K. Kamada, I. Nagata, S. Yamashita, miR-195, miR-455-3p and miR-10a( *) are implicated in acquired temozolomide resistance in glioblastoma multiforme cells. Cancer Lett 296, 241–248 (2010)CrossRefPubMedGoogle Scholar
  206. 206.
    C. Bruyere, L. Abeloos, D. Lamoral-Theys, R. Senetta, V. Mathieu, M. Le Mercier, R.E. Kast, P. Cassoni, G. Vandenbussche, R. Kiss, F. Lefranc, Temozolomide modifies caveolin-1 expression in experimental malignant gliomas in vitro and in vivo. Transl Oncol 4, 92–100 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  207. 207.
    K. Quann, D.M. Gonzales, I. Mercier, C. Wang, F. Sotgia, R.G. Pestell, M.P. Lisanti, J.F. Jasmin, Caveolin-1 is a negative regulator of tumor growth in glioblastoma and modulates chemosensitivity to temozolomide. Cell Cycle 12, 1510–1520 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  208. 208.
    C.A. DI, G. Carrabba, G. Lanfranchi, C. Menghetti, P. Rampini, M. Caroli, Continuous tamoxifen and dose-dense temozolomide in recurrent glioblastoma. Anticancer Res 33, 3383–3389 (2013)Google Scholar
  209. 209.
    A.M. Hui, W. Zhang, W. Chen, D. Xi, B. Purow, G.C. Friedman, H.A. Fine, Agents with selective estrogen receptor (ER) modulator activity induce apoptosis in vitro and in vivo in ER-negative glioma cells. Cancer Res 64, 9115–9123 (2004)CrossRefPubMedGoogle Scholar
  210. 210.
    W. He, R. Liu, S.H. Yang, F. Yuan, Chemotherapeutic effect of tamoxifen on temozolomide-resistant gliomas. Anti-Cancer Drugs 26, 293–300 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  211. 211.
    Z. Wang, X. Zhang, P. Shen, B.W. Loggie, Y. Chang, T.F. Deuel, Identification, cloning, and expression of human estrogen receptor-alpha36, a novel variant of human estrogen receptor-alpha66. Biochem Biophys Res Commun 336, 1023–1027 (2005)CrossRefPubMedGoogle Scholar
  212. 212.
    L. Shi, B. Dong, Z. Li, Y. Lu, T. Ouyang, J. Li, T. Wang, Z. Fan, T. Fan, B. Lin, Z. Wang, Y. Xie, Expression of ER-{alpha}36, a novel variant of estrogen receptor {alpha}, and resistance to tamoxifen treatment in breast cancer. J Clin Oncol 27, 3423–3429 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  213. 213.
    Y. Liu, L. Huang, X. Guan, H. Li, Q.Q. Zhang, C. Han, Y.J. Wang, C. Wang, Y. Zhang, C. Qu, J. Liu, W. Zou, ER-alpha36, a novel variant of ERalpha, is involved in the regulation of tamoxifen-sensitivity of glioblastoma cells. Steroids 111, 127–133 (2016)CrossRefPubMedGoogle Scholar
  214. 214.
    J.H. Lin, M. Yamazaki, Role of P-glycoprotein in pharmacokinetics: Clinical implications. Clin Pharmacokinet 42, 59–98 (2003)CrossRefPubMedPubMedCentralGoogle Scholar
  215. 215.
    J. Jodoin, M. Demeule, L. Fenart, R. Cecchelli, S. Farmer, K.J. Linton, C.F. Higgins, R. Beliveau, P-glycoprotein in blood-brain barrier endothelial cells: Interaction and oligomerization with caveolins. J Neurochem 87, 1010–1023 (2003)CrossRefPubMedGoogle Scholar
  216. 216.
    P.L. Golden, W.M. Pardridge, P-glycoprotein on astrocyte foot processes of unfixed isolated human brain capillaries. Brain Res 819, 143–146 (1999)CrossRefPubMedGoogle Scholar
  217. 217.
    Y. Zhang, S.X. Wang, J.W. Ma, H.Y. Li, J.C. Ye, S.M. Xie, B. Du, X.Y. Zhong, EGCG inhibits properties of glioma stem-like cells and synergizes with temozolomide through downregulation of P-glycoprotein inhibition. J Neuro-Oncol 121, 41–52 (2015)CrossRefGoogle Scholar
  218. 218.
    J.L. Munoz, N.D. Walker, K.W. Scotto, P. Rameshwar, Temozolomide competes for P-glycoprotein and contributes to chemoresistance in glioblastoma cells. Cancer Lett 367, 69–75 (2015)CrossRefPubMedGoogle Scholar
  219. 219.
    P.T. Ronaldson, M. Bendayan, D. Gingras, M. Piquette-Miller, R. Bendayan, Cellular localization and functional expression of P-glycoprotein in rat astrocyte cultures. J Neurochem 89, 788–800 (2004)CrossRefPubMedGoogle Scholar
  220. 220.
    F. Schlachetzki, W.M. Pardridge, P-glycoprotein and caveolin-1alpha in endothelium and astrocytes of primate brain. Neuroreport 14, 2041–2046 (2003)CrossRefPubMedGoogle Scholar
  221. 221.
    M.D. Walker, S.B. Green, D.P. Byar, E. Alexander Jr., U. Batzdorf, W.H. Brooks, W.E. Hunt, C.S. MacCarty, M.S. Mahaley Jr., J. Mealey Jr., G. Owens, J. Ransohoff 2nd, J.T. Robertson, W.R. Shapiro, K.R. Smith Jr., C.B. Wilson, T.A. Strike, Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med 303, 1323–1329 (1980)CrossRefPubMedGoogle Scholar
  222. 222.
    J. Mahmood, S.R. Zaveri, S.C. Murti, A.A. Alexander, C.Q. Connors, H.D. Shukla, Z. Vujaskovic, Caveolin-1: A novel prognostic biomarker of radioresistance in cancer. Int J Radiat Biol 92, 747–753 (2016)CrossRefPubMedGoogle Scholar
  223. 223.
    H. Zhu, J. Yue, Z. Pan, H. Wu, Y. Cheng, H. Lu, X. Ren, M. Yao, Z. Shen, J.M. Yang, Involvement of Caveolin-1 in repair of DNA damage through both homologous recombination and non-homologous end joining. PLoS One 5, e12055 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
  224. 224.
    N. McLaughlin, B. Annabi, M. Bouzeghrane, A. Temme, J.P. Bahary, R. Moumdjian, R. Beliveau, The Survivin-mediated radioresistant phenotype of glioblastomas is regulated by RhoA and inhibited by the green tea polyphenol (−)-epigallocatechin-3-gallate. Brain Res 1071, 1–9 (2006)CrossRefPubMedGoogle Scholar
  225. 225.
    A. Chakravarti, G.G. Zhai, M. Zhang, R. Malhotra, D.E. Latham, M.A. Delaney, P. Robe, U. Nestler, Q. Song, J. Loeffler, Survivin enhances radiation resistance in primary human glioblastoma cells via caspase-independent mechanisms. Oncogene 23, 7494–7506 (2004)CrossRefPubMedGoogle Scholar
  226. 226.
    P. Dahan, J. Martinez Gala, C. Delmas, S. Monferran, L. Malric, D. Zentkowski, V. Lubrano, C. Toulas, E. Cohen-Jonathan Moyal, A. Lemarie, Ionizing radiations sustain glioblastoma cell dedifferentiation to a stem-like phenotype through survivin: Possible involvement in radioresistance. Cell Death Dis 5, e1543 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  227. 227.
    M.A. Forget, J.L. Voorhees, S.L. Cole, D. Dakhlallah, I.L. Patterson, A.C. Gross, L. Moldovan, X. Mo, R. Evans, C.B. Marsh, T.D. Eubank, Macrophage colony-stimulating factor augments Tie2-expressing monocyte differentiation, angiogenic function, and recruitment in a mouse model of breast cancer. PLoS One 9, e98623 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  228. 228.
    A. Backen, A.G. Renehan, A.R. Clamp, C. Berzuini, C. Zhou, A. Oza, S. Bannoo, S.J. Scherer, R.E. Banks, C. Dive, G.C. Jayson, The combination of circulating Ang1 and Tie2 levels predicts progression-free survival advantage in bevacizumab-treated patients with ovarian cancer. Clin Cancer Res 20, 4549–4558 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  229. 229.
    Y. Piao, S.Y. Park, V. Henry, B.D. Smith, N. Tiao, D.L. Flynn, J.F. de Groot, Novel MET/TIE2/VEGFR2 inhibitor altiratinib inhibits tumor growth and invasiveness in bevacizumab-resistant glioblastoma mouse models. Neuro-Oncology 18, 1230–1241 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  230. 230.
    O.H. Lee, J. Xu, J. Fueyo, G.N. Fuller, K.D. Aldape, M.M. Alonso, Y. Piao, T.J. Liu, F.F. Lang, B.N. Bekele, C. Gomez-Manzano, Expression of the receptor tyrosine kinase Tie2 in neoplastic glial cells is associated with integrin beta1-dependent adhesion to the extracellular matrix. Mol Cancer Res 4, 915–926 (2006)CrossRefPubMedGoogle Scholar
  231. 231.
    E. Bogdanovic, N. Coombs, D.J. Dumont, Oligomerized Tie2 localizes to clathrin-coated pits in response to angiopoietin-1. Histochem Cell Biol 132, 225–237 (2009)CrossRefPubMedGoogle Scholar
  232. 232.
    M.B. Hossain, R. Shifat, D.G. Johnson, M.T. Bedford, K.R. Gabrusiewicz, N. Cortes-Santiago, X. Luo, Z. Lu, R. Ezhilarasan, E.P. Sulman, H. Jiang, S.S. Li, F.F. Lang, J. Tyler, M.C. Hung, J. Fueyo, C. Gomez-Manzano, TIE2-mediated tyrosine phosphorylation of H4 regulates DNA damage response by recruiting ABL1. Sci Adv 2, e1501290 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  233. 233.
    M.B. Hossain, R. Shifat, J. Li, X. Luo, K.R. Hess, Y. Rivera-Molina, F. Puerta Martinez, H. Jiang, F.F. Lang, M.C. Hung, J. Fueyo, C. Gomez-Manzano, TIE2 associates with Caveolae and regulates Caveolin-1 to promote their nuclear translocation. Mol Cell Biol 37 (2017)Google Scholar
  234. 234.
    V. Barresi, S. Cerasoli, G. Paioli, E. Vitarelli, G. Giuffre, G. Guiducci, G. Tuccari, G. Barresi, Caveolin-1 in meningiomas: Expression and clinico-pathological correlations. Acta Neuropathol 112, 617–626 (2006)CrossRefPubMedGoogle Scholar
  235. 235.
    V. Barresi, S. Cerasoli, G. Tuccari, Correlative evidence that tumor cell-derived caveolin-1 mediates angiogenesis in meningiomas. Neuropathology 28, 472–478 (2008)CrossRefPubMedGoogle Scholar
  236. 236.
    S. Sharma, S. Ray, S. Mukherjee, A. Moiyadi, E. Sridhar, S. Srivastava, Multipronged quantitative proteomic analyses indicate modulation of various signal transduction pathways in human meningiomas. Proteomics 15, 394–407 (2015)CrossRefPubMedGoogle Scholar
  237. 237.
    M. Aarhus, O. Bruland, H.A. Saetran, S.J. Mork, M. Lund-Johansen, P.M. Knappskog, Global gene expression profiling and tissue microarray reveal novel candidate genes and down-regulation of the tumor suppressor gene CAV1 in sporadic vestibular schwannomas. Neurosurgery 67, 998–1019; discussion 1019 (2010)CrossRefPubMedGoogle Scholar
  238. 238.
    M. Torres-Martin, L. Lassaletta, J. San-Roman-Montero, J.M. De Campos, A. Isla, J. Gavilan, B. Melendez, G.R. Pinto, R.R. Burbano, J.S. Castresana, J.A. Rey, Microarray analysis of gene expression in vestibular schwannomas reveals SPP1/MET signaling pathway and androgen receptor deregulation. Int J Oncol 42, 848–862 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  239. 239.
    P. Cassoni, L. Daniele, E. Maldi, L. Righi, V. Tavaglione, S. Novello, M. Volante, G.V. Scagliotti, M. Papotti, Caveolin-1 expression in lung carcinoma varies according to tumour histotype and is acquired de novo in brain metastases. Histopathology 55, 20–27 (2009)CrossRefPubMedGoogle Scholar
  240. 240.
    W.T. Chiu, H.T. Lee, F.J. Huang, K.D. Aldape, J. Yao, P.S. Steeg, C.Y. Chou, Z. Lu, K. Xie, S. Huang, Caveolin-1 upregulation mediates suppression of primary breast tumor growth and brain metastases by stat3 inhibition. Cancer Res 71, 4932–4943 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
  241. 241.
    E. Duregon, R. Senetta, A. Pittaro, L. Verdun di Cantogno, G. Stella, P. De Blasi, M. Zorzetto, C. Mantovani, M. Papotti, P. Cassoni, CAVEOLIN-1 expression in brain metastasis from lung cancer predicts worse outcome and radioresistance, irrespective of tumor histotype. Oncotarget 6, 29626–29636 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  242. 242.
    I.R. Whittle, C. Smith, P. Navoo, D. Collie, Meningiomas. Lancet 363, 1535–1543 (2004)CrossRefPubMedGoogle Scholar
  243. 243.
    G. Yang, J. Addai, T.M. Wheeler, A. Frolov, B.J. Miles, D. Kadmon, T.C. Thompson, Correlative evidence that prostate cancer cell-derived caveolin-1 mediates angiogenesis. Hum Pathol 38, 1688–1695 (2007)CrossRefPubMedGoogle Scholar
  244. 244.
    H.J. Joo, D.K. Oh, Y.S. Kim, K.B. Lee, S.J. Kim, Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prognosis in clear cell renal cell carcinoma. BJU Int 93, 291–296 (2004)CrossRefPubMedGoogle Scholar
  245. 245.
    V. Barresi, Angiogenesis in meningiomas. Brain Tumor Pathol 28, 99–106 (2011)CrossRefPubMedGoogle Scholar
  246. 246.
    S.H. Chang, D. Feng, J.A. Nagy, T.E. Sciuto, A.M. Dvorak, H.F. Dvorak, Vascular permeability and pathological angiogenesis in caveolin-1-null mice. Am J Pathol 175, 1768–1776 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
  247. 247.
    K. Podar, R. Shringarpure, Y.T. Tai, M. Simoncini, M. Sattler, K. Ishitsuka, P.G. Richardson, T. Hideshima, D. Chauhan, K.C. Anderson, Caveolin-1 is required for vascular endothelial growth factor-triggered multiple myeloma cell migration and is targeted by bortezomib. Cancer Res 64, 7500–7506 (2004)CrossRefPubMedGoogle Scholar
  248. 248.
    T.D. Anderson, L.A. Loevner, D.C. Bigelow, N. Mirza, Prevalence of unsuspected acoustic neuroma found by magnetic resonance imaging. Otolaryngol Head Neck Surg 122, 643–646 (2000)CrossRefPubMedGoogle Scholar
  249. 249.
    J. Sainz, D.P. Huynh, K. Figueroa, N.K. Ragge, M.E. Baser, S.M. Pulst, Mutations of the neurofibromatosis type 2 gene and lack of the gene product in vestibular schwannomas. Hum Mol Genet 3, 885–891 (1994)CrossRefPubMedGoogle Scholar
  250. 250.
    C.O. Hanemann, B. Bartelt-Kirbach, R. Diebold, K. Kampchen, S. Langmesser, T. Utermark, Differential gene expression between human schwannoma and control Schwann cells. Neuropathol Appl Neurobiol 32, 605–614 (2006)CrossRefPubMedGoogle Scholar
  251. 251.
    D.B. Welling, J.M. Lasak, E. Akhmametyeva, B. Ghaheri, L.S. Chang, cDNA microarray analysis of vestibular schwannomas. Otol Neurotol 23, 736–748 (2002)CrossRefPubMedGoogle Scholar
  252. 252.
    P. Eser Ocak, I. Dogan, U. Ocak, C. Dinc, M.K. Baskaya, Facial nerve outcome and extent of resection in cystic versus solid vestibular schwannomas in radiosurgery era. Neurosurg Focus 44, E3 (2018)CrossRefPubMedGoogle Scholar
  253. 253.
    P. Eser Ocak, I. Dogan, S. Sayyahmelli and M.K. Baskaya, in Vestibular Schwannoma Surgery, (2019), p. 105–133Google Scholar
  254. 254.
    A. Grande-Garcia, A. Echarri, J. de Rooij, N.B. Alderson, C.M. Waterman-Storer, J.M. Valdivielso, M.A. del Pozo, Caveolin-1 regulates cell polarization and directional migration through Src kinase and rho GTPases. J Cell Biol 177, 683–694 (2007)CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society for Cellular Oncology 2019

Authors and Affiliations

  • Pinar Eser Ocak
    • 1
  • Umut Ocak
    • 1
  • Jiping Tang
    • 1
  • John H. Zhang
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Department of Physiology and PharmacologyLoma Linda University School of MedicineLoma LindaUSA
  2. 2.Department of AnesthesiologyLoma Linda University School of MedicineLoma LindaUSA
  3. 3.Department of NeurologyLoma Linda University School of MedicineLoma LindaUSA
  4. 4.Department of NeurosurgeryLoma Linda University School of MedicineLoma LindaUSA

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