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Current insights into the metastasis of epithelial ovarian cancer - hopes and hurdles

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Abstract

Background

Ovarian cancer is the most lethal gynecologic cancer and the fifth leading cause of cancer-related mortality in women worldwide. Despite various attempts to improve the diagnosis and therapy of ovarian cancer patients, the survival rate for these patients is still dismal, mainly because most of them are diagnosed at a late stage. Up to 90% of ovarian cancers arise from neoplastic transformation of ovarian surface epithelial cells, and are usually referred to as epithelial ovarian cancer (EOC). Unlike most human cancers, which are disseminated through blood-borne metastatic routes, EOC has traditionally been thought to be disseminated through direct migration of ovarian tumor cells to the peritoneal cavity and omentum via peritoneal fluid. It has recently been shown, however, that EOC can also be disseminated through blood-borne metastatic routes, challenging previous thoughts about ovarian cancer metastasis.

Conclusions

Here, we review our current understanding of the most updated cellular and molecular mechanisms underlying EOC metastasis and discuss in more detail two main metastatic routes of EOC, i.e., transcoelomic metastasis and hematogenous metastasis. The emerging concept of blood-borne EOC metastasis has led to exploration of the significance of circulating tumor cells (CTCs) as novel and non-invasive prognostic markers in this daunting cancer. We also evaluate the role of tumor stroma, including cancer associated fibroblasts (CAFs), tumor associated macrophages (TAMs), endothelial cells, adipocytes, dendritic cells and extracellular matrix (ECM) components in EOC growth and metastasis. Lastly, we discuss therapeutic approaches for targeting EOC. Unraveling the mechanisms underlying EOC metastasis will open up avenues to the design of new therapeutic options. For instance, understanding the molecular mechanisms involved in the hematogenous metastasis of EOC, the biology of CTCs, and the detailed mechanisms through which EOC cells take advantage of stromal cells may help to find new opportunities for targeting EOC metastasis.

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References

  1. R.L. Siegel, K.D. Miller, A. Jemal, Cancer Statistics, 2017. CA Cancer J. Clin. 67, 7–30 (2017)

    PubMed  Google Scholar 

  2. Cancer Stat Facts: Ovarian Cancer 2019 [June 2019]. Available from: https://seer.cancer.gov/statfacts/html/ovary.html

  3. L.H. Smith, C.R. Morris, S. Yasmeen, A. Parikh-Patel, R.D. Cress, P.S. Romano, Ovarian cancer: can we make the clinical diagnosis earlier? Cancer 104, 1398–1407 (2005)

    PubMed  Google Scholar 

  4. T.L. Yeung, C.S. Leung, K.P. Yip, C.L.A. Yeung, S.T. Wong, S.C. Mok, Cellular and molecular processes in ovarian cancer metastasis. A review in the theme: cell and molecular processes in cancer metastasis. Am. J. Phys. Cell Phys. 309, C444–C456 (2015)

    CAS  Google Scholar 

  5. N. Auersperg, A.S. Wong, K.C. Choi, S.K. Kang, P.C. Leung, Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr. Rev. 22, 255–288 (2001)

    CAS  PubMed  Google Scholar 

  6. C.L. Chaffer, R.A. Weinberg, A perspective on cancer cell metastasis. Science 331, 1559–1564 (2011)

    CAS  PubMed  Google Scholar 

  7. M. Yousefi, T. Bahrami, A. Salmaninejad, R. Nosrati, P. Ghaffari, S.H. Ghaffari, Lung cancer-associated brain metastasis: Molecular mechanisms and therapeutic options. Cell. Oncol. 40, 419–441 (2017)

  8. K.R. Hess, G.R. Varadhachary, S.H. Taylor, W. Wei, M.N. Raber, R. Lenzi, J.L. Abbruzzese, Metastatic patterns in adenocarcinoma. Cancer 106, 1624–1633 (2006)

    PubMed  Google Scholar 

  9. J. Budczies, M. von Winterfeld, F. Klauschen, M. Bockmayr, J.K. Lennerz, C. Denkert, T. Wolf, A. Warth, M. Dietel, I. Anagnostopoulos, W. Weichert, D. Wittschieber, A. Stenzinger, The landscape of metastatic progression patterns across major human cancers. Oncotarget 6, 570–583 (2015)

    PubMed  Google Scholar 

  10. A.C. Obenauf, J. Massague, Surviving at a distance: organ specific metastasis. Trends Cancer 1, 76–91 (2015)

    PubMed  PubMed Central  Google Scholar 

  11. O. Akin, E. Sala, C.S. Moskowitz, N. Ishill, R.A. Soslow, D.S. Chi, H. Hricak, Perihepatic metastases from ovarian cancer: sensitivity and specificity of CT for the detection of metastases with and those without liver parenchymal invasion. Radiology 248, 511–517 (2008)

    PubMed  Google Scholar 

  12. I.J. Fidler, G. Poste, The “seed and soil” hypothesis revisited. Lancet Oncol. 9, 808 (2008)

  13. R.R. Langley, I.J. Fidler, The seed and soil hypothesis revisited--the role of tumor-stroma interactions in metastasis to different organs. Int. J. Cancer 128, 2527–2535 (2011)

    CAS  PubMed  PubMed Central  Google Scholar 

  14. I.J. Fidler, The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat. Rev. Cancer 3, 453–458 (2003)

    CAS  PubMed  Google Scholar 

  15. N. Ribelles, A. Santonja, B. Pajares, C. Llácer, E. Alba, The seed and soil hypothesis revisited: Current state of knowledge of inherited genes on prognosis in breast cancer. Cancer Treat. Rev. 40, 293–299 (2014)

    PubMed  Google Scholar 

  16. S. Pradeep, S.W. Kim, S.Y. Wu, M. Nishimura, P. Chaluvally-Raghavan, T. Miyake, C.V. Pecot, S.J. Kim, H.J. Choi, F.Z. Bischoff, J.A. Mayer, L. Huang, A.M. Nick, C.S. Hall, C. Rodriguez-Aguayo, B. Zand, H.J. Dalton, T. Arumugam, H.J. Lee, H.D. Han, M.S. Cho, R. Rupaimoole, L.S. Mangala, V. Sehgal, S.C. Oh, J. Liu, J.S. Lee, R.L. Coleman, P. Ram, G. Lopez-Berestein, I.J. Fidler, A.K. Sood, Hematogenous metastasis of ovarian cancer: rethinking mode of spread. Cancer Cell 26, 77–91 (2014)

    CAS  PubMed  PubMed Central  Google Scholar 

  17. K. Hibbs, K.M. Skubitz, S.E. Pambuccian, R.C. Casey, K.M. Burleson, T.R. Oegema, J.J. Thiele, S.M. Grindle, R.L. Bliss, A.P.N. Skubitz, Differential Gene Expression in Ovarian Carcinoma : Identification of Potential Biomarkers. Am. J. Pathol. 165, 397–414 (2004)

    CAS  PubMed  PubMed Central  Google Scholar 

  18. J. Bayani, J.D. Brenton, P.F. Macgregor, B. Beheshti, M. Albert, D. Nallainathan, J. Karaskova, B. Rosen, J. Murphy, S. Laframboise, B. Zanke, J.A. Squire, Parallel analysis of sporadic primary ovarian carcinomas by spectral karyotyping, comparative genomic hybridization, and expression microarrays. Cancer Res. 62, 3466–3476 (2002)

    CAS  PubMed  Google Scholar 

  19. A. Fishman, E. Shalom-Paz, M. Fejgin, E. Gaber, M. Altaras, A. Amiel, Comparing the genetic changes detected in the primary and secondary tumor sites of ovarian cancer using comparative genomic hybridization. Int. J. Gynecol. Cancer 15, 261–266 (2005)

    CAS  PubMed  Google Scholar 

  20. D. Caserta, M. Benkhalifa, M. Baldi, F. Fiorentino, M. Qumsiyeh, M. Moscarini, Genome profiling of ovarian adenocarcinomas using pangenomic BACs microarray comparative genomic hybridization. Mol. Cytogenet. 1, 10 (2008)

    PubMed  PubMed Central  Google Scholar 

  21. D.S. Tan, R. Agarwal, S.B. Kaye, Mechanisms of transcoelomic metastasis in ovarian cancer. Lancet Oncol. 7, 925–934 (2006)

    PubMed  Google Scholar 

  22. E. Lengyel, Ovarian cancer development and metastasis. Am. J. Pathol. 177, 1053–1064 (2010)

    PubMed  PubMed Central  Google Scholar 

  23. D. Tarin, J.E. Price, M.G. Kettlewell, R.G. Souter, A.C. Vass, B. Crossley, Mechanisms of human tumor metastasis studied in patients with peritoneovenous shunts. Cancer Res. 44, 3584–3592 (1984)

    CAS  PubMed  Google Scholar 

  24. K.M. Nieman, H.A. Kenny, C.V. Penicka, A. Ladanyi, R. Buell-Gutbrod, M.R. Zillhardt, I.L. Romero, M.S. Carey, G.B. Mills, G.S. Hotamisligil, S.D. Yamada, M.E. Peter, K. Gwin, E. Lengyel, Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat. Med. 17, 1498 (2011)

    CAS  PubMed  PubMed Central  Google Scholar 

  25. T.R. Adib, S. Henderson, C. Perrett, D. Hewitt, D. Bourmpoulia, J. Ledermann, C. Boshoff, Predicting biomarkers for ovarian cancer using gene-expression microarrays. Br. J. Cancer 90, 686–692 (2004)

    CAS  PubMed  PubMed Central  Google Scholar 

  26. J. Bayani, J.D. Brenton, P.F. Macgregor, B. Beheshti, M. Albert, D. Nallainathan, J. Karaskova, B. Rosen, J. Murphy, S. Laframboise, B. Zanke, J.A. Squire, Parallel analysis of sporadic primary ovarian carcinomas by spectral karyotyping, comparative genomic hybridization, and expression microarrays. Cancer Res. 62, 3466–3476 (2002)

    CAS  PubMed  Google Scholar 

  27. O. Israeli, W.H. Gotlieb, E. Friedman, J. Korach, E. Friedman, B. Goldman, A. Zeltser, G. Ben-Baruch, S. Rienstein, A. Aviram-Goldring, Genomic analyses of primary and metastatic serous epithelial ovarian cancer. Cancer Genet. Cytogenet. 154, 16–21 (2004)

    CAS  PubMed  Google Scholar 

  28. A. Fishman, E. Shalom-Paz, M. Fejgin, E. Gaber, M. Altaras, A. Amiel, Comparing the genetic changes detected in the primary and secondary tumor sites of ovarian cancer using comparative genomic hybridization. Int. J. Gynecol. Cancer 15, 261–266 (2005)

    CAS  PubMed  Google Scholar 

  29. F. van Roy, G. Berx, The cell-cell adhesion molecule E-cadherin. Cell. Mol. Life Sci. 65, 3756–3788 (2008)

    CAS  PubMed  Google Scholar 

  30. M. Rosso, B. Majem, L. Devis, L. Lapyckyj, M.J. Besso, M. Llaurado, M.F. Abascal, M.L. Matos, L. Lanau, J. Castellvi, J.L. Sanchez, A. Perez Benavente, A. Gil-Moreno, J. Reventos, A. Santamaria Margalef, M. Rigau, M.H. Vazquez-Levin, E-cadherin: A determinant molecule associated with ovarian cancer progression, dissemination and aggressiveness. PLoS One 12, e0184439 (2017)

    PubMed  PubMed Central  Google Scholar 

  31. T. Imai, A. Horiuchi, C. Wang, K. Oka, S. Ohira, T. Nikaido, I. Konishi, Hypoxia attenuates the expression of E-Cadherin via up-regulation of SNAIL in ovarian carcinoma cells. Am. J. Pathol. 163, 1437–1447 (2003)

  32. C. Faleiro-Rodrigues, I. Macedo-Pinto, D. Pereira, V.M. Ferreira, C.S. Lopes, Association of E-cadherin and beta-catenin immunoexpression with clinicopathologic features in primary ovarian carcinomas. Hum. Pathol. 35, 663–669 (2004)

    CAS  PubMed  Google Scholar 

  33. S. Heerboth, G. Housman, M. Leary, M. Longacre, S. Byler, K. Lapinska, A. Willbanks, S. Sarkar, EMT and tumor metastasis. Clin. Transl. Med. 4, 6 (2015)

  34. S. Zhang, C. Balch, M.W. Chan, H.C. Lai, D. Matei, J.M. Schilder, P.S. Yan, T.H. Huang, K.P. Nephew, Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res. 68, 4311–4320 (2008)

    CAS  PubMed  PubMed Central  Google Scholar 

  35. D. Vergara, B. Merlot, J.P. Lucot, P. Collinet, D. Vinatier, I. Fournier, M. Salzet, Epithelial-mesenchymal transition in ovarian cancer. Cancer Lett. 291, 59–66 (2010)

    CAS  PubMed  Google Scholar 

  36. A.N. Corps, H.M. Sowter, S.K. Smith, Hepatocyte growth factor stimulates motility, chemotaxis and mitogenesis in ovarian carcinoma cells expressing high levels of c-MET. Int. J. Cancer 73, 151–155 (1997)

    CAS  PubMed  Google Scholar 

  37. M. Korpal, Y. Kang, The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal transition and cancer metastasis. RNA Biol. 5, 115–119 (2008)

    CAS  PubMed  Google Scholar 

  38. C. Wu, J. Cipollone, S. Maines-Bandiera, C. Tan, A. Karsan, N. Auersperg, C.D. Roskelley, The morphogenic function of E-cadherin-mediated adherens junctions in epithelial ovarian carcinoma formation and progression. Differentiation 76, 193–205 (2008)

    CAS  PubMed  Google Scholar 

  39. L. Seguin, J.S. Desgrosellier, S.M. Weis, D.A. Cheresh, Integrins and cancer: regulators of cancer stemness, metastasis, and drug resistance. Trends Cell Biol. 25, 234–240 (2015)

    CAS  PubMed  PubMed Central  Google Scholar 

  40. N. Ahmed, F. Pansino, R. Clyde, P. Murthi, M.A. Quinn, G.E. Rice, M.V. Agrez, S. Mok, M.S. Baker, Overexpression of alpha(v)beta6 integrin in serous epithelial ovarian cancer regulates extracellular matrix degradation via the plasminogen activation cascade. Carcinogenesis 23, 237–244 (2002)

    CAS  PubMed  Google Scholar 

  41. R.P. Czekay, D.J. Loskutoff, Unexpected role of plasminogen activator inhibitor 1 in cell adhesion and detachment. Exp. Biol. Med. (Maywood) 229, 1090–1096 (2004)

  42. C.P. Carmignani, T.A. Sugarbaker, C.M. Bromley, P.H. Sugarbaker, Intraperitoneal cancer dissemination: mechanisms of the patterns of spread. Cancer Metastasis Rev. 22, 465–472 (2003)

    PubMed  Google Scholar 

  43. L. Xu, J. Yoneda, C. Herrera, J. Wood, J.J. Killion, I.J. Fidler, Inhibition of malignant ascites and growth of human ovarian carcinoma by oral administration of a potent inhibitor of the vascular endothelial growth factor receptor tyrosine kinases. Int. J. Oncol. 16, 445–454 (2000)

    CAS  PubMed  Google Scholar 

  44. D. Belotti, P. Paganoni, L. Manenti, A. Garofalo, S. Marchini, G. Taraboletti, R. Giavazzi, Matrix metalloproteinases (MMP9 and MMP2) induce the release of vascular endothelial growth factor (VEGF) by ovarian carcinoma cells: implications for ascites formation. Cancer Res. 63, 5224–5229 (2003)

    CAS  PubMed  Google Scholar 

  45. R.C. Casey, A.P. Skubitz, CD44 and beta1 integrins mediate ovarian carcinoma cell migration toward extracellular matrix proteins. Clin. Exp. Metastasis 18, 67–75 (2000)

    CAS  PubMed  Google Scholar 

  46. F. Balkwill, Cancer and the chemokine network. Nat. Rev. Cancer 4, 540–550 (2004)

    CAS  PubMed  Google Scholar 

  47. K. Gawrychowski, G. Szewczyk, E. Skopińska-Różewska, M. Małecki, E. Barcz, P. Kamiński, M. Miedzińska-Maciejewska, W. Śmiertka, D. Szukiewicz, P. Skopiński, the angiogenic activity of ascites in the course of ovarian cancer as a marker of disease progression. Dis. Markers 2014, 683757 (2014)

  48. N. Ahmed, K.L. Stenvers, Getting to know ovarian cancer ascites: opportunities for targeted therapy-based translational research. Front. Oncol. 3, 256 (2013)

    PubMed  PubMed Central  Google Scholar 

  49. J.C. Pease, M. Brewer, J.S. Tirnauer, Spontaneous spheroid budding from monolayers: a potential contribution to ovarian cancer dissemination. Biol. Open 1, 622–628 (2012)

  50. K.M. Burleson, R.C. Casey, K.M. Skubitz, S.E. Pambuccian, T.R. Oegema Jr., A.P. Skubitz, Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers. Gynecol. Oncol. 93, 170–181 (2004)

    CAS  PubMed  Google Scholar 

  51. M. Wintzell, E. Hjerpe, E. Avall Lundqvist, M. Shoshan, Protein markers of cancer-associated fibroblasts and tumor-initiating cells reveal subpopulations in freshly isolated ovarian cancer ascites. BMC Cancer 12, 359 (2012)

    CAS  PubMed  PubMed Central  Google Scholar 

  52. B. Davidson, C.G. Trope, R. Reich, The role of the tumor stroma in ovarian cancer. Front. Oncol. 4, 104 (2014)

    PubMed  PubMed Central  Google Scholar 

  53. E.K. Colvin, Tumor-associated macrophages contribute to tumor progression in ovarian cancer. Front. Oncol. 4, 137 (2014)

    PubMed  PubMed Central  Google Scholar 

  54. V.M. Abrahams, S.L. Straszewski, M. Kamsteeg, B. Hanczaruk, P.E. Schwartz, T.J. Rutherford, G. Mor, Epithelial ovarian cancer cells secrete functional Fas ligand. Cancer Res. 63, 5573–5581 (2003)

    CAS  PubMed  Google Scholar 

  55. A. Frankel, R. Buckman, R.S. Kerbel, Abrogation of taxol-induced G2-M arrest and apoptosis in human ovarian cancer cells grown as multicellular tumor spheroids. Cancer Res. 57, 2388–2393 (1997)

    CAS  PubMed  Google Scholar 

  56. Q. Cai, L. Yan, Y. Xu, Anoikis resistance is a critical feature of highly aggressive ovarian cancer cells. Oncogene 34, 3315–3324 (2015)

    CAS  PubMed  Google Scholar 

  57. A. Tajbakhsh, M. Rivandi, S. Abedini, A. Pasdar, A. Sahebkar, Regulators and mechanisms of anoikis in triple-negative breast cancer (TNBC): A review. Crit. Rev. Oncol. Hematol. 140, 17–27 (2019)

    PubMed  Google Scholar 

  58. K.W. Cheng, J.P. Lahad, W.-l. Kuo, A. Lapuk, K. Yamada, N. Auersperg, J. Liu, K. Smith-McCune, K.H. Lu, D. Fishman, J.W. Gray, G.B. Mills, The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers. Nat. Med. 10, 1251 (2004)

    CAS  PubMed  Google Scholar 

  59. S. Salceda, T. Tang, M. Kmet, A. Munteanu, M. Ghosh, R. Macina, W. Liu, G. Pilkington, J. Papkoff, The immunomodulatory protein B7-H4 is overexpressed in breast and ovarian cancers and promotes epithelial cell transformation. Exp. Cell Res. 306, 128–141 (2005)

    CAS  PubMed  Google Scholar 

  60. C.A. Witz, I.A. Montoya-Rodriguez, S. Cho, V.E. Centonze, L.F. Bonewald, R.S. Schenken, Composition of the extracellular matrix of the peritoneum. J. Soc. Gynecol. Investig. 8, 299–304 (2001)

    CAS  PubMed  Google Scholar 

  61. 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 α(5)-integrin, which is a therapeutic target. Cancer Res. 68, 2329–2339 (2008)

    CAS  PubMed  PubMed Central  Google Scholar 

  62. A.A. Kamat, M. Fletcher, L.M. Gruman, P. Mueller, A. Lopez, C.N. Landen Jr., L. Han, D.M. Gershenson, A.K. Sood, The clinical relevance of stromal matrix metalloproteinase expression in ovarian cancer. Clin. Cancer Res. 12, 1707–1714 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  63. M. Egeblad, Z. Werb, New functions for the matrix metalloproteinases in cancer progression. Nat. Rev. Cancer 2, 161–174 (2002)

    CAS  PubMed  Google Scholar 

  64. H.A. Kenny, S. Kaur, L.M. Coussens, E. Lengyel, The initial steps of ovarian cancer cell metastasis are mediated by MMP-2 cleavage of vitronectin and fibronectin. J. Clin. Invest. 118, 1367–1379 (2008)

    CAS  PubMed  PubMed Central  Google Scholar 

  65. A. Rump, Y. Morikawa, M. Tanaka, S. Minami, N. Umesaki, M. Takeuchi, A. Miyajima, Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion. J. Biol. Chem. 279, 9190–9198 (2004)

    CAS  PubMed  Google Scholar 

  66. X. Fang, M. Schummer, M. Mao, S. Yu, F.H. Tabassam, R. Swaby, Y. Hasegawa, J.L. Tanyi, R. LaPushin, A. Eder, R. Jaffe, J. Erickson, G.B. Mills, Lysophosphatidic acid is a bioactive mediator in ovarian cancer. Biochim. Biophys. Acta 1582, 257–264 (2002)

    CAS  PubMed  Google Scholar 

  67. D.A. Fishman, Y. Liu, S.M. Ellerbroek, M.S. Stack, Lysophosphatidic acid promotes matrix metalloproteinase (MMP) activation and MMP-dependent invasion in ovarian cancer cells. Cancer Res. 61, 3194–3199 (2001)

    CAS  PubMed  Google Scholar 

  68. T.B. Pustilnik, V. Estrella, J.R. Wiener, M. Mao, A. Eder, M.A. Watt, R.C. Bast Jr., G.B. Mills, Lysophosphatidic acid induces urokinase secretion by ovarian cancer cells. Clin. Cancer Res. 5, 3704–3710 (1999)

    CAS  PubMed  Google Scholar 

  69. D. Bian, S. Su, C. Mahanivong, R.K. Cheng, Q. Han, Z.K. Pan, P. Sun, S. Huang, Lysophosphatidic acid stimulates ovarian cancer cell migration via a Ras-MEK kinase 1 pathway. Cancer Res. 64, 4209–4217 (2004)

    CAS  PubMed  Google Scholar 

  70. R. Agarwal, T. D'Souza, P.J. Morin, Claudin-3 and claudin-4 expression in ovarian epithelial cells enhances invasion and is associated with increased matrix metalloproteinase-2 activity. Cancer Res. 65, 7378–7385 (2005)

    CAS  PubMed  Google Scholar 

  71. T. Yagyu, H. Kobayashi, H. Matsuzaki, K. Wakahara, T. Kondo, N. Kurita, H. Sekino, K. Inagaki, Enhanced spontaneous metastasis in bikunin-deficient mice. Int. J. Cancer 118, 2322–2328 (2006)

    CAS  PubMed  Google Scholar 

  72. S. Cai, P. Zhang, S. Dong, L. Li, J. Cai, M. Xu, Downregulation of SPINK13 Promotes Metastasis by Regulating uPA in Ovarian Cancer Cells. Cell. Physiol. Biochem. 45, 1061–1071 (2018)

    CAS  PubMed  Google Scholar 

  73. X.Y. Zhang, R. Pettengell, N. Nasiri, V. Kalia, A.G. Dalgleish, D.P. Barton, Characteristics and growth patterns of human peritoneal mesothelial cells: comparison between advanced epithelial ovarian cancer and non-ovarian cancer sources. J. Soc. Gynecol. Investig. 6, 333–340 (1999)

    CAS  PubMed  Google Scholar 

  74. A.K. Mitra, C.Y. Chiang, P. Tiwari, S. Tomar, K.M. Watters, M.E. Peter, E. Lengyel, Microenvironment-induced downregulation of miR-193b drives ovarian cancer metastasis. Oncogene 34, 5923–5932 (2015)

    CAS  PubMed  PubMed Central  Google Scholar 

  75. S. Tomar, J.P. Plotnik, J. Haley, J. Scantland, S. Dasari, Z. Sheikh, R. Emerson, D. Lenz, P.C. Hollenhorst, A.K. Mitra, ETS1 induction by the microenvironment promotes ovarian cancer metastasis through focal adhesion kinase. Cancer Lett. 414, 190–204 (2018)

    CAS  PubMed  Google Scholar 

  76. R.S. Freedman, M. Deavers, J. Liu, E. Wang, Peritoneal inflammation – A microenvironment for Epithelial Ovarian Cancer (EOC). J. Transl. Med. 2, 23 (2004)

  77. A. Feki, P. Berardi, G. Bellingan, A. Major, K.H. Krause, P. Petignat, R. Zehra, S. Pervaiz, I. Irminger-Finger, Dissemination of intraperitoneal ovarian cancer: Discussion of mechanisms and demonstration of lymphatic spreading in ovarian cancer model. Crit. Rev. Oncol. Hematol. 72, 1–9 (2009)

    PubMed  Google Scholar 

  78. G. Balbi, M.A. Manganaro, A. Monteverde, I. Landino, C. Franzese, F. Gioia, Ovarian cancer: lymph node metastases. European J. Gynaecol. Oncol. 30, 289–291 (2009)

    CAS  Google Scholar 

  79. S.S. Chen, Survival of ovarian carcinoma with or without lymph node metastasis. Gynecol. Oncol. 27, 368–372 (1987)

    CAS  PubMed  Google Scholar 

  80. C. Bachmann, R. Bachmann, F. Fend, D. Wallwiener, Incidence and impact of lymph node metastases in advanced ovarian cancer: Implications for surgical treatment. J. Cancer 7, 2241–2246 (2016)

  81. K. Matsuo, T.B. Sheridan, K. Yoshino, T. Miyake, K.E. Hew, D.D. Im, N.B. Rosenshein, S. Mabuchi, T. Enomoto, T. Kimura, A.K. Sood, L.D. Roman, Significance of lymphovascular space invasion in epithelial ovarian cancer. Cancer Med. 1, 156–164 (2012)

    PubMed  PubMed Central  Google Scholar 

  82. M. Chen, Y. Jin, Y. Bi, Y. Li, Y. Shan, L. Pan, Prognostic significance of lymphovascular space invasion in epithelial ovarian cancer. J. Cancer 6, 412–419 (2015)

    PubMed  PubMed Central  Google Scholar 

  83. P. Wimberger, S. Hauch, M. Lustig, R. Kimmig, S. Kasimir-Bauer, Detection and molecular profiling of circulating tumor cells in patients with primary ovarian cancer. Cancer Res. 68, 965 (2008)

    Google Scholar 

  84. K.G. Phillips, C.R. Velasco, J. Li, A. Kolatkar, M. Luttgen, K. Bethel, B. Duggan, P. Kuhn, O.J. McCarty, Optical quantification of cellular mass, volume, and density of circulating tumor cells identified in an ovarian cancer patient. Front. Oncol. 2, 72 (2012)

    PubMed  PubMed Central  Google Scholar 

  85. L. Cui, J. Kwong, C.C. Wang, Prognostic value of circulating tumor cells and disseminated tumor cells in patients with ovarian cancer: a systematic review and meta-analysis. J Ovarian Res. 8, 38 (2015)

    PubMed  PubMed Central  Google Scholar 

  86. M.C. Lim, S. Kang, K.S. Lee, S.S. Han, S.J. Park, S.S. Seo, S.Y. Park, The clinical significance of hepatic parenchymal metastasis in patients with primary epithelial ovarian cancer. Gynecol. Oncol. 112, 28–34 (2009)

    PubMed  Google Scholar 

  87. L.G. Coffman, D. Burgos-Ojeda, R. Wu, K. Cho, S. Bai, R.J. Buckanovich, New models of hematogenous ovarian cancer metastasis demonstrate preferential spread to the ovary and a requirement for the ovary for abdominal dissemination. Transl. Res. 175, 92–102.e2 (2016)

  88. P.C. Bailey, S.S. Martin, Insights on CTC biology and clinical impact emerging from advances in capture technology. Cells 8, pii: E553 (2019)

  89. M. Yousefi, P. Ghaffari, R. Nosrati, S. Dehghani, A. Salmaninejad, Y.J. Abarghan, S.H. Ghaffari, Prognostic and therapeutic significance of circulating tumor cells in patients with lung cancer. Cell Oncol. 43, 31–49 (2020)

  90. S.A. Joosse, T.M. Gorges, K. Pantel, Biology, detection, and clinical implications of circulating tumor cells. EMBO Mol. Med. 7, 1–11 (2015)

    CAS  PubMed  Google Scholar 

  91. M. Yousefi, R. Nosrati, A. Salmaninejad, S. Dehghani, A. Shahryari, A. Saberi, Organ-specific metastasis of breast cancer: molecular and cellular mechanisms underlying lung metastasis. Cell Oncol. 41, 123–140 (2018)

  92. Y. Wang, Y. Zhou, Z. Hu, The functions of circulating tumor cells in early diagnosis and surveillance during cancer advancement. J. Trans. Intern Med. 5, 135–138 (2017)

  93. C. Paoletti, D.F. Hayes, Circulating tumor cells. Adv. Exp. Med. Biol. 882, 235–258 (2016)

  94. M. Cristofanilli, G.T. Budd, M.J. Ellis, A. Stopeck, J. Matera, M.C. Miller, J.M. Reuben, G.V. Doyle, W.J. Allard, L.W. Terstappen, D.F. Hayes, Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N. Engl. J. Med. 351, 781–791 (2004)

    CAS  PubMed  Google Scholar 

  95. M.C. Miller, G.V. Doyle, L.W. Terstappen, Significance of circulating tumor cells detected by the CellSearch system in patients with metastatic breast colorectal and prostate cancer. J. Oncol. 2010, 617421 (2010)

  96. D.T. Miyamoto, L.V. Sequist, R.J. Lee, Circulating tumour cells-monitoring treatment response in prostate cancer. Nat. Rev. Clin. Oncol. 11, 401–412 (2014)

    CAS  PubMed  Google Scholar 

  97. B. Aktas, S. Kasimir-Bauer, M. Heubner, R. Kimmig, P. Wimberger, Molecular profiling and prognostic relevance of circulating tumor cells in the blood of ovarian cancer patients at primary diagnosis and after platinum-based chemotherapy. Int. J. Gynecol. Cancer 21, 822–830 (2011)

    PubMed  Google Scholar 

  98. E. Obermayr, D.C. Castillo-Tong, D. Pils, P. Speiser, I. Braicu, T. Van Gorp, S. Mahner, J. Sehouli, I. Vergote, R. Zeillinger, Molecular characterization of circulating tumor cells in patients with ovarian cancer improves their prognostic significance -- a study of the OVCAD consortium. Gynecol. Oncol. 128, 15–21 (2013)

    CAS  PubMed  Google Scholar 

  99. M. Sang, X. Wu, X. Fan, M. Sang, X. Zhou, N. Zhou, Multiple MAGE-A genes as surveillance marker for the detection of circulating tumor cells in patients with ovarian cancer. Biomarkers 19, 34–42 (2014)

    CAS  PubMed  Google Scholar 

  100. A.K. Mitra, Ovarian cancer metastasis: a unique mechanism of dissemination (InTech, Tumor Metastasis, 2016)

    Google Scholar 

  101. D. Hanahan, L.M. Coussens, Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 21, 309–322 (2012)

    CAS  PubMed  Google Scholar 

  102. P. Nilendu, S. C. Sarode, D. Jahagirdar, I. Tandon, S. Patil, G. S. Sarode, J. K. Pal, N. K. Sharma. Mutual concessions and compromises between stromal cells and cancer cells: driving tumor development and drug resistance. Cell. Oncol. 41, 353–67 (2018)

  103. M.A. Swartz, N. Iida, E.W. Roberts, S. Sangaletti, M.H. Wong, F.E. Yull, L.M. Coussens, Y.A. DeClerck, Tumor microenvironment complexity: emerging roles in cancer therapy. Cancer Res. 72, 2473–2480 (2012)

    CAS  PubMed  PubMed Central  Google Scholar 

  104. A. Ghoneum, H. Afify, Z. Salih, M. Kelly, N. Said. Role of tumor microenvironment in the pathobiology of ovarian cancer: Insights and therapeutic opportunities. Cancer Med. 10, 5047-5056 (2018)

  105. J.A. Joyce, Therapeutic targeting of the tumor microenvironment. Cancer Cell 7, 513–520 (2005)

    CAS  PubMed  Google Scholar 

  106. P. Cirri, P. Chiarugi, Cancer associated fibroblasts: the dark side of the coin. Am. J. Cancer Res. 1, 482–497 (2011)

    CAS  PubMed  PubMed Central  Google Scholar 

  107. N. Eiro, L. Gonzalez, A. Martinez-Ordonez, B. Fernandez-Garcia, L. O. Gonzalez, S. Cid, F. Dominguez, R. Perez-Fernandez, F. J. Vizoso. Cancer-associated fibroblasts affect breast cancer cell gene expression, invasion and angiogenesis. Cell. Oncol. 41, 369–78 (2018)

  108. A. Orimo, R.A. Weinberg, Stromal fibroblasts in cancer: a novel tumor-promoting cell type. Cell Cycle 5, 1597–1601 (2006)

    CAS  PubMed  Google Scholar 

  109. I.G. Schauer, A.K. Sood, S. Mok, J. Liu, Cancer-associated fibroblasts and their putative role in potentiating the initiation and development of epithelial ovarian cancer. Neoplasia (New York, NY) 13, 393–405 (2011)

    CAS  Google Scholar 

  110. R. Kalluri, M. Zeisberg, Fibroblasts in cancer. Nat. Rev. Cancer 6, 392–401 (2006)

    CAS  PubMed  Google Scholar 

  111. M. Yanez-Mo, E. Lara-Pezzi, R. Selgas, M. Ramirez-Huesca, C. Dominguez-Jimenez, J.A. Jimenez-Heffernan, A. Aguilera, J.A. Sanchez-Tomero, M.A. Bajo, V. Alvarez, M.A. Castro, G. del Peso, A. Cirujeda, C. Gamallo, F. Sanchez-Madrid, M. Lopez-Cabrera, Peritoneal dialysis and epithelial-to-mesenchymal transition of mesothelial cells. N. Engl. J. Med. 348, 403–413 (2003)

    PubMed  Google Scholar 

  112. P. Sandoval, J.A. Jimenez-Heffernan, A. Rynne-Vidal, M.L. Perez-Lozano, A. Gilsanz, V. Ruiz-Carpio, R. Reyes, J. Garcia-Bordas, K. Stamatakis, J. Dotor, P.L. Majano, M. Fresno, C. Cabanas, M. Lopez-Cabrera, Carcinoma-associated fibroblasts derive from mesothelial cells via mesothelial-to-mesenchymal transition in peritoneal metastasis. J. Pathol. 231, 517–531 (2013)

  113. A. Rynne-Vidal, C. L. Au-Yeung, J. A. Jimenez-Heffernan, M. L. Perez-Lozano, L. Cremades-Jimeno, C. Barcena, I. Cristobal-Garcia, C. Fernandez-Chacon, T. L. Yeung, S. C. Mok, P. Sandoval. Mesothelial-to-mesenchymal transition as a possible therapeutic target in peritoneal metastasis of ovarian cancer. J Pathol. 242, 140–51 (2017)

  114. B. Dirat, L. Bochet, M. Dabek, D. Daviaud, S. Dauvillier, B. Majed, Y.Y. Wang, A. Meulle, B. Salles, S. Le Gonidec, I. Garrido, G. Escourrou, P. Valet, C. Muller, Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res. 71, 2455–2465 (2011)

    CAS  PubMed  Google Scholar 

  115. L. Bochet, C. Lehuede, S. Dauvillier, Y.Y. Wang, B. Dirat, V. Laurent, C. Dray, R. Guiet, I. Maridonneau-Parini, S. Le Gonidec, B. Couderc, G. Escourrou, P. Valet, C. Muller, Adipocyte-derived fibroblasts promote tumor progression and contribute to the desmoplastic reaction in breast cancer. Cancer Res. 73, 5657–5668 (2013)

    CAS  PubMed  Google Scholar 

  116. E. Zoico, E. Darra, V. Rizzatti, S. Budui, G. Franceschetti, G. Mazzali, A.P. Rossi, F. Fantin, M. Menegazzi, S. Cinti, M. Zamboni, Adipocytes WNT5a mediated dedifferentiation: a possible target in pancreatic cancer microenvironment. Oncotarget 7, 20223–20235 (2016)

    PubMed  PubMed Central  Google Scholar 

  117. H.M. Lawler, C.M. Underkofler, P.A. Kern, C. Erickson, B. Bredbeck, N. Rasouli, Adipose tissue hypoxia, inflammation, and fibrosis in obese insulin-sensitive and obese insulin-resistant subjects. J. Clin. Endocrinol. Metab. 101, 1422–1428 (2016)

  118. J. Cai, H. Tang, L. Xu, X. Wang, C. Yang, S. Ruan, J. Guo, S. Hu, Z. Wang, Fibroblasts in omentum activated by tumor cells promote ovarian cancer growth, adhesion and invasiveness. Carcinogenesis 33, 20–29 (2012)

    CAS  PubMed  Google Scholar 

  119. A. Ghoneum, H. Afify, Z. Salih, M. Kelly, N. Said, Role of tumor microenvironment in ovarian cancer pathobiology. Oncotarget 9, 22832–22849 (2018)

    PubMed  PubMed Central  Google Scholar 

  120. T. Dong, D. Yang, R. Li, L. Zhang, H. Zhao, Y. Shen, X. Zhang, B. Kong, L. Wang, PGRN promotes migration and invasion of epithelial ovarian cancer cells through an epithelial mesenchymal transition program and the activation of cancer associated fibroblasts. Exp. Mol. Pathol. 100, 17–25 (2016)

    CAS  PubMed  Google Scholar 

  121. M. Di Francesco, S. D'Ascenzo, M.G. Palmerini, G. Macchiarelli, G. Carta, V. Dolo, Ovarian cancer-derived extracellular vesicles affect normal human fibroblast behavior AU - Giusti. Ilaria. Cancer Biology & Therapy 19, 722–734 (2018)

    Google Scholar 

  122. V. Sundararajan, F.H. Sarkar, T.S. Ramasamy, The multifaceted role of exosomes in cancer progression: diagnostic and therapeutic implications [corrected]. Cell. Oncol. 41, 223–252 (2018)

  123. A.K. Mitra, M. Zillhardt, Y. Hua, P. Tiwari, A.E. Murmann, M.E. Peter, E. Lengyel, MicroRNAs reprogram normal fibroblasts into cancer-associated fibroblasts in ovarian cancer. Cancer Discov. 2, 1100–1108 (2012)

  124. Y. Zhang, H. Tang, J. Cai, T. Zhang, J. Guo, D. Feng, Z. Wang, Ovarian cancer-associated fibroblasts contribute to epithelial ovarian carcinoma metastasis by promoting angiogenesis, lymphangiogenesis and tumor cell invasion. Cancer Lett. 303, 47–55 (2011)

    CAS  PubMed  Google Scholar 

  125. S. Liekens, D. Schols, S. Hatse, CXCL12-CXCR4 axis in angiogenesis, metastasis and stem cell mobilization. Curr. Pharm. Des. 16, 3903–3920 (2010)

    CAS  PubMed  Google Scholar 

  126. T.L. Yeung, C.S. Leung, K.K. Wong, G. Samimi, M.S. Thompson, J. Liu, T.M. Zaid, S. Ghosh, M.J. Birrer, S.C. Mok, TGF-beta modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment. Cancer Res. 73, 5016–5028 (2013)

    CAS  PubMed  PubMed Central  Google Scholar 

  127. A. Salmaninejad, S.F. Valilou, A. Soltani, S. Ahmadi, Y.J. Abarghan, R.J. Rosengren, A. Sahebkar, Tumor-associated macrophages: role in cancer development and therapeutic implications. Cell. Oncol. 42, 591–608 (2019)

  128. A. Mantovani, P. Allavena, A. Sica, F. Balkwill, Cancer-related inflammation. Nature 454, 436–444 (2008)

    CAS  PubMed  Google Scholar 

  129. K. Kawamura, Y. Komohara, K. Takaishi, H. Katabuchi, M. Takeya, Detection of M2 macrophages and colony-stimulating factor 1 expression in serous and mucinous ovarian epithelial tumors. Pathol. Int. 59, 300–305 (2009)

    PubMed  Google Scholar 

  130. E. Schutyser, S. Struyf, P. Proost, G. Opdenakker, G. Laureys, B. Verhasselt, L. Peperstraete, I. Van de Putte, A. Saccani, P. Allavena, A. Mantovani, J. Van Damme, Identification of biologically active chemokine isoforms from ascitic fluid and elevated levels of CCL18/pulmonary and activation-regulated chemokine in ovarian carcinoma. J. Biol. Chem. 277, 24584–24593 (2002)

    CAS  PubMed  Google Scholar 

  131. L.S. Ojalvo, C.A. Whittaker, J.S. Condeelis, J.W. Pollard, Gene expression analysis of macrophages that facilitate tumor invasion supports a role for Wnt-signaling in mediating their activity in primary mammary tumors. J. Immunol. 184, 702–712 (2010)

    CAS  PubMed  Google Scholar 

  132. M. Torroella-Kouri, R. Silvera, D. Rodriguez, R. Caso, A. Shatry, S. Opiela, D. Ilkovitch, R.A. Schwendener, V. Iragavarapu-Charyulu, Y. Cardentey, N. Strbo, D.M. Lopez, Identification of a subpopulation of macrophages in mammary tumor-bearing mice that are neither M1 nor M2 and are less differentiated. Cancer Res. 69, 4800–4809 (2009)

    CAS  PubMed  Google Scholar 

  133. S.K. Biswas, L. Gangi, S. Paul, T. Schioppa, A. Saccani, M. Sironi, B. Bottazzi, A. Doni, B. Vincenzo, F. Pasqualini, L. Vago, M. Nebuloni, A. Mantovani, A. Sica, A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood 107, 2112–2122 (2006)

    CAS  PubMed  Google Scholar 

  134. L.S. Ojalvo, W. King, D. Cox, J.W. Pollard, High-density gene expression analysis of tumor-associated macrophages from mouse mammary tumors. Am. J. Pathol. 174, 1048–1064 (2009)

    CAS  PubMed  PubMed Central  Google Scholar 

  135. B.Z. Qian, J.W. Pollard, Macrophage diversity enhances tumor progression and metastasis. Cell 141, 39–51 (2010)

    CAS  PubMed  PubMed Central  Google Scholar 

  136. D. Hambardzumyan, D.H. Gutmann, H. Kettenmann, The role of microglia and macrophages in glioma maintenance and progression. Nat. Neurosci. 19, 20 (2015)

    Google Scholar 

  137. V. Kumar, P. Cheng, T. Condamine, S. Mony, L.R. Languino, J.C. McCaffrey, N. Hockstein, M. Guarino, G. Masters, E. Penman, F. Denstman, X. Xu, D.C. Altieri, H. Du, C. Yan, D.I. Gabrilovich, CD45 phosphatase inhibits STAT3 transcriptionfFactor activity in myeloid cells and promotes tumor-associated macrophage differentiation. Immunity 44, 303–315 (2016)

  138. A. Mantovani, F. Marchesi, A. Malesci, L. Laghi, P. Allavena, Tumour-associated macrophages as treatment targets in oncology. Nat. Rev. Clin. Oncol. 14, 399–416 (2017)

    CAS  PubMed  PubMed Central  Google Scholar 

  139. S.K. Biswas, A. Mantovani, Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat. Immunol. 11, 889–896 (2010)

    CAS  PubMed  Google Scholar 

  140. R. Clark, V. Krishnan, M. Schoof, I. Rodriguez, B. Theriault, M. Chekmareva, C. Rinker-Schaeffer, Milky spots promote ovarian cancer metastatic colonization of peritoneal adipose in experimental models. Am. J. Pathol. 183, 576–591 (2013)

    CAS  PubMed  PubMed Central  Google Scholar 

  141. T.M. Robinson-Smith, I. Isaacsohn, C.A. Mercer, M. Zhou, N. Van Rooijen, N. Husseinzadeh, M.M. McFarland-Mancini, A.F. Drew, Macrophages mediate inflammation-enhanced metastasis of ovarian tumors in mice. Cancer Res. 67, 5708–5716 (2007)

    CAS  PubMed  Google Scholar 

  142. J. Liu, X. Geng, Y. Li, Milky spots: omental functional units and hotbeds for peritoneal cancer metastasis. Tumour Biol. 37, 5715–5726 (2016)

  143. X. Yuan, J. Zhang, D. Li, Y. Mao, F. Mo, W. Du, X. Ma, Prognostic significance of tumor-associated macrophages in ovarian cancer: A meta-analysis. Gynecol. Oncol. 147, 181–187 (2017)

    CAS  PubMed  Google Scholar 

  144. L.S. Ojalvo, E.D. Thompson, T.L. Wang, A.K. Meeker, I.M. Shih, A.N. Fader, A. Cimino-Mathews, L.A. Emens, Tumor-associated macrophages and the tumor immune microenvironment of primary and recurrent epithelial ovarian cancer. Hum. Pathol. 74, 135–147 (2018)

  145. S. Huang, M. Van Arsdall, S. Tedjarati, M. McCarty, W. Wu, R. Langley, I.J. Fidler, Contributions of stromal metalloproteinase-9 to angiogenesis and growth of human ovarian carcinoma in mice. J. Natl. Cancer Inst. 94, 1134–1142 (2002)

    CAS  PubMed  Google Scholar 

  146. X. Wang, M. Deavers, R. Patenia, R.L. Bassett Jr., P. Mueller, Q. Ma, E. Wang, R.S. Freedman, Monocyte/macrophage and T-cell infiltrates in peritoneum of patients with ovarian cancer or benign pelvic disease. J. Transl. Med. 4, 30 (2006)

    PubMed  PubMed Central  Google Scholar 

  147. S.F. Schoppmann, A. Fenzl, K. Nagy, S. Unger, G. Bayer, S. Geleff, M. Gnant, R. Horvat, R. Jakesz, P. Birner, VEGF-C expressing tumor-associated macrophages in lymph node positive breast cancer: impact on lymphangiogenesis and survival. Surgery 139, 839–846 (2006)

    PubMed  Google Scholar 

  148. L. Liu, X. Wang, X. Li, X. Wu, M. Tang, X. Wang, Upregulation of IGF1 by tumor-associated macrophages promotes the proliferation and migration of epithelial ovarian cancer cells. Oncol. Rep. 39, 818–826 (2018)

    CAS  PubMed  Google Scholar 

  149. N. Nishida, H. Yano, T. Nishida, T. Kamura, M. Kojiro, Angiogenesis in cancer. Vasc. Health Risk Manag. 2, 213–219 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  150. M. Rajabi, S.A. Mousa, The Role of Angiogenesis in Cancer Treatment. Biomedicines 5, 34 (2017)

    PubMed Central  Google Scholar 

  151. T. Tonini, F. Rossi, P.P. Claudio, Molecular basis of angiogenesis and cancer. Oncogene 22, 6549–6556 (2003)

    CAS  PubMed  Google Scholar 

  152. A.K. Olsson, A. Dimberg, J. Kreuger, L. Claesson-Welsh, VEGF receptor signalling - in control of vascular function. Nat. Rev. Mol. Cell Biol. 7, 359–371 (2006)

    CAS  PubMed  Google Scholar 

  153. S. Dehghani, R. Nosrati, M. Yousefi, A. Nezami, F. Soltani, S.M. Taghdisi, K. Abnous, M. Alibolandi, M. Ramezani, Aptamer-based biosensors and nanosensors for the detection of vascular endothelial growth factor (VEGF): A review. Biosens. Bioelectron. 110, 23–37 (2018)

    CAS  PubMed  Google Scholar 

  154. M.J. Birrer, M.E. Johnson, K. Hao, K.K. Wong, D.C. Park, A. Bell, W.R. Welch, R.S. Berkowitz, S.C. Mok, Whole genome oligonucleotide-based array comparative genomic hybridization analysis identified fibroblast growth factor 1 as a prognostic marker for advanced-stage serous ovarian adenocarcinomas. J. Clin. Oncol. 25, 2281–2287 (2007)

    CAS  PubMed  Google Scholar 

  155. T.M. Zaid, T.L. Yeung, M.S. Thompson, C.S. Leung, T. Harding, N.N. Co, R.S. Schmandt, S.Y. Kwan, C. Rodriguez-Aguay, G. Lopez-Berestein, A.K. Sood, K.K. Wong, M.J. Birrer, S.C. Mok, Identification of FGFR4 as a potential therapeutic target for advanced-stage, high-grade serous ovarian cancer. Clin. Cancer Res. 19, 809–820 (2013)

    CAS  PubMed  PubMed Central  Google Scholar 

  156. W. Wei, S.C. Mok, E. Oliva, S.H. Kim, G. Mohapatra, M.J. Birrer, FGF18 as a prognostic and therapeutic biomarker in ovarian cancer. J. Clin. Invest. 123, 4435–4448 (2013)

    CAS  PubMed  PubMed Central  Google Scholar 

  157. L. Hu, L. Cong, Fibroblast growth factor 19 is correlated with an unfavorable prognosis and promotes progression by activating fibroblast growth factor receptor 4 in advanced-stage serous ovarian cancer. Oncol. Rep. 34, 2683–2691 (2015)

    CAS  PubMed  Google Scholar 

  158. X. Wang, Q. Zhu, Y. Lin, L. Wu, X. Wu, K. Wang, Q. He, C. Xu, X. Wan, X. Wang, Crosstalk between TEMs and endothelial cells modulates angiogenesis and metastasis via IGF1-IGF1R signalling in epithelial ovarian cancer. Br. J. Cancer 117, 1371–1382 (2017)

    CAS  PubMed  PubMed Central  Google Scholar 

  159. J. Yang, Y. Wang, Z. Zeng, L. Qiao, L. Zhuang, Q. Gao, D. Ma, X. Huang, Smad4 deletion in blood vessel endothelial cells promotes ovarian cancer metastasis. Int. J. Oncol. 50, 1693–1700 (2017)

    CAS  PubMed  Google Scholar 

  160. M. Yin, H.J. Zhou, J. Zhang, C. Lin, H. Li, X. Li, Y. Li, H. Zhang, D.G. Breckenridge, W. Ji, W. Min, ASK1-dependent endothelial cell activation is critical in ovarian cancer growth and metastasis. JCI Insight 2 (2017)

  161. J. Hoarau-Vechot, C. Touboul, N. Halabi, M. Blot-Dupin, R. Lis, C. Abi Khalil, S. Rafii, A. Rafii, J. Pasquier, Akt-activated endothelium promotes ovarian cancer proliferation through notch activation. J. Transl. Med. 17, 194 (2019)

    PubMed  PubMed Central  Google Scholar 

  162. A. Nowicka, F.C. Marini, T.N. Solley, P.B. Elizondo, Y. Zhang, H.J. Sharp, R. Broaddus, M. Kolonin, S.C. Mok, M.S. Thompson, W.A. Woodward, K. Lu, B. Salimian, D. Nagrath, A.H. Klopp, Human omental-derived adipose stem cells increase ovarian cancer proliferation, migration, and chemoresistance. PLoS One 8, e81859 (2013)

    PubMed  PubMed Central  Google Scholar 

  163. P. Sartipy, D.J. Loskutoff, Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc. Natl. Acad. Sci. U. S. A. 100, 7265–7270 (2003)

    CAS  PubMed  PubMed Central  Google Scholar 

  164. G.K. Reeves, K. Pirie, V. Beral, J. Green, E. Spencer, D. Bull, Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. Bmj 335, 1134 (2007)

    PubMed  PubMed Central  Google Scholar 

  165. A. Ghasemi, J. Saeidi, M. Azimi-Nejad, S. I. Hashemy. Leptin-induced signaling pathways in cancer cell migration and invasion. Cell. Oncol. 42, 243–60 (2019)

  166. A.G. Renehan, M. Tyson, M. Egger, R.F. Heller, M. Zwahlen, Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371, 569–578 (2008)

    PubMed  Google Scholar 

  167. E.E. Calle, C. Rodriguez, K. Walker-Thurmond, M.J. Thun, Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. New Eng. J. Med. 348, 1625–1638 (2003)

  168. E.S. Trombetta, I. Mellman, Cell biology of antigen processing in vitro and in vivo. Annu. Rev. Immunol. 23, 975–1028 (2005)

    CAS  PubMed  Google Scholar 

  169. F. Veglia, D.I. Gabrilovich, Dendritic cells in cancer: the role revisited. Curr. Opin. Immunol. 45, 43–51 (2017)

    CAS  PubMed  PubMed Central  Google Scholar 

  170. E. Segura, S. Amigorena, Inflammatory dendritic cells in mice and humans. Trends Immunol. 34, 440–445 (2013)

    CAS  PubMed  Google Scholar 

  171. E. Daro, B. Pulendran, K. Brasel, M. Teepe, D. Pettit, D.H. Lynch, D. Vremec, L. Robb, K. Shortman, H.J. McKenna, C.R. Maliszewski, E. Maraskovsky, Polyethylene glycol-modified GM-CSF expands CD11b(high)CD11c(high) but notCD11b(low)CD11c(high) murine dendritic cells in vivo: a comparative analysis with Flt3 ligand. J. Immunol. 165, 49–58 (2000)

    CAS  PubMed  Google Scholar 

  172. S. Menezes, D. Melandri, G. Anselmi, T. Perchet, J. Loschko, J. Dubrot, R. Patel, E.L. Gautier, S. Hugues, M.P. Longhi, J.Y. Henry, S.A. Quezada, G. Lauvau, A.M. Lennon-Dumenil, E. Gutierrez-Martinez, A. Bessis, E. Gomez-Perdiguero, C.E. Jacome-Galarza, H. Garner, F. Geissmann, R. Golub, M.C. Nussenzweig, P. Guermonprez, The heterogeneity of Ly6C(hi) monocytes controls their differentiation into iNOS(+) macrophages or monocyte-derived dendritic cells. Immunity 45, 1205–1218 (2016)

    CAS  PubMed  PubMed Central  Google Scholar 

  173. S. Kuhn, E.J. Hyde, J. Yang, F.J. Rich, J.L. Harper, J.R. Kirman, F. Ronchese, Increased numbers of monocyte-derived dendritic cells during successful tumor immunotherapy with immune-activating agents. J. Immunol. 191, 1984–1992 (2013)

    CAS  PubMed  Google Scholar 

  174. E. Segura, M. Touzot, A. Bohineust, A. Cappuccio, G. Chiocchia, A. Hosmalin, M. Dalod, V. Soumelis, S. Amigorena, Human inflammatory dendritic cells induce Th17 cell differentiation. Immunity 38, 336–348 (2013)

    CAS  PubMed  Google Scholar 

  175. B. Ruffell, D. Chang-Strachan, V. Chan, A. Rosenbusch, C.M. Ho, N. Pryer, D. Daniel, E.S. Hwang, H.S. Rugo, L.M. Coussens, Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. Cancer Cell. 26, 623–637 (2014)

    CAS  PubMed  PubMed Central  Google Scholar 

  176. A. Salmaninejad, S.F. Valilou, A.G. Shabgah, S. Aslani, M. Alimardani, A. Pasdar, A. Sahebkar, PD-1/PD-L1 pathway: Basic biology and role in cancer immunotherapy. J. Cell. Physiol. 234, 16824–16837 (2019)

    CAS  PubMed  Google Scholar 

  177. H. Salmon, J. Idoyaga, A. Rahman, M. Leboeuf, R. Remark, S. Jordan, M. Casanova-Acebes, M. Khudoynazarova, J. Agudo, N. Tung, S. Chakarov, C. Rivera, B. Hogstad, M. Bosenberg, D. Hashimoto, S. Gnjatic, N. Bhardwaj, A.K. Palucka, B.D. Brown, J. Brody, F. Ginhoux, M. Merad, Expansion and activation of CD103(+) dendritic cell progenitors at the tumor site enhances tumor responses to therapeutic PD-L1 and BRAF inhibition. Immunity 44, 924–938 (2016)

  178. D.L. Herber, W. Cao, Y. Nefedova, S.V. Novitskiy, S. Nagaraj, V.A. Tyurin, A. Corzo, H.I. Cho, E. Celis, B. Lennox, S.C. Knight, T. Padhya, T.V. McCaffrey, J.C. McCaffrey, S. Antonia, M. Fishman, R.L. Ferris, V.E. Kagan, D.I. Gabrilovich, Lipid accumulation and dendritic cell dysfunction in cancer. Nat. Med. 16, 880–886 (2010)

    CAS  PubMed  PubMed Central  Google Scholar 

  179. J.R. Cubillos-Ruiz, P.C. Silberman, M.R. Rutkowski, S. Chopra, A. Perales-Puchalt, M. Song, S. Zhang, S.E. Bettigole, D. Gupta, K. Holcomb, L.H. Ellenson, T. Caputo, A.-H. Lee, J.R. Conejo-Garcia, L.H. Glimcher, ER stress sensor XBP1 controls anti-tumor immunity by disrupting dendritic cell homeostasis. Cell 161, 1527–1538 (2015)

  180. K. Dass, A. Ahmad, A.S. Azmi, S.H. Sarkar, F.H. Sarkar, Evolving role of uPA/uPAR system in human cancers. Cancer Treat. Rev. 34, 122–136 (2008)

    CAS  PubMed  Google Scholar 

  181. L. Wang, M.C. Madigan, H. Chen, F. Liu, K.I. Patterson, J. Beretov, P.M. O'Brien, Y. Li, Expression of urokinase plasminogen activator and its receptor in advanced epithelial ovarian cancer patients. Gynecol. Oncol. 114, 265–272 (2009)

    CAS  PubMed  Google Scholar 

  182. J. Dorn, N. Harbeck, R. Kates, A. Gkazepis, A. Scorilas, A. Soosaipillai, E. Diamandis, M. Kiechle, B. Schmalfeldt, M. Schmitt, Impact of expression differences of kallikrein-related peptidases and of uPA and PAI-1 between primary tumor and omentum metastasis in advanced ovarian cancer. Ann. Oncol. 22, 877–883 (2011)

    CAS  PubMed  Google Scholar 

  183. C. Alberti, P. Pinciroli, B. Valeri, R. Ferri, A. Ditto, K. Umezawa, M. Sensi, S. Canevari, A. Tomassetti, Ligand-dependent EGFR activation induces the co-expression of IL-6 and PAI-1 via the NFkB pathway in advanced-stage epithelial ovarian cancer. Oncogene 31, 4139–4149 (2012)

    CAS  PubMed  Google Scholar 

  184. P.A. van Dam, A. Coelho, C. Rolfo, Is there a role for urokinase-type plasminogen activator inhibitors as maintenance therapy in patients with ovarian cancer? Eur. J. Surg. Oncol. 43, 252–257 (2017)

    PubMed  Google Scholar 

  185. B. Schmalfeldt, D. Prechtel, K. Harting, K. Spathe, S. Rutke, E. Konik, R. Fridman, U. Berger, M. Schmitt, W. Kuhn, E. Lengyel, Increased expression of matrix metalloproteinases (MMP)-2, MMP-9, and the urokinase-type plasminogen activator is associated with progression from benign to advanced ovarian cancer. Clin. Cancer Res. 7, 2396–2404 (2001)

    CAS  PubMed  Google Scholar 

  186. M. Maatta, M. Santala, Y. Soini, A. Talvensaari-Mattila, T. Turpeenniemi-Hujanen, Matrix metalloproteinases 2 and 9 and their tissue inhibitors in low malignant potential ovarian tumors. Tumour Biol. 25, 188–192 (2004)

    CAS  PubMed  Google Scholar 

  187. S. Sillanpaa, M. Anttila, K. Voutilainen, K. Ropponen, T. Turpeenniemi-Hujanen, U. Puistola, R. Tammi, M. Tammi, R. Sironen, S. Saarikoski, V.M. Kosma, Prognostic significance of matrix metalloproteinase-9 (MMP-9) in epithelial ovarian cancer. Gynecol. Oncol. 104, 296–303 (2007)

    CAS  PubMed  Google Scholar 

  188. H. Nishikawa, Y. Ozaki, T. Nakanishi, K. Blomgren, T. Tada, A. Arakawa, K. Suzumori, The role of cathepsin B and cystatin C in the mechanisms of invasion by ovarian cancer. Gynecol. Oncol. 92, 881–886 (2004)

    CAS  PubMed  Google Scholar 

  189. J.L. Brun, A. Cortez, F. Commo, S. Uzan, R. Rouzier, E. Darai, Serous and mucinous ovarian tumors express different profiles of MMP-2, −7, −9, MT1-MMP, and TIMP-1 and -2. Int. J. Oncol. 33, 1239–1246 (2008)

    CAS  PubMed  Google Scholar 

  190. Z.S. Wu, Q. Wu, J.H. Yang, H.Q. Wang, X.D. Ding, F. Yang, X.C. Xu, Prognostic significance of MMP-9 and TIMP-1 serum and tissue expression in breast cancer. Int. J. Cancer 122, 2050–2056 (2008)

    CAS  PubMed  Google Scholar 

  191. L.S. Downs Jr., P.H. Lima, R.L. Bliss, C.H. Blomquist, Cathepsins B and D activity and activity ratios in normal ovaries, benign ovarian neoplasms, and epithelial ovarian cancer. J. Soc. Gynecol. Investig. 12, 539–544 (2005)

    CAS  PubMed  Google Scholar 

  192. Q. Pan, S. Yang, Y. Wei, F. Sun, Z. Li, SP1 acts as a key factor, contributes to upregulation of ADAM23 expression under serum deprivation. Biochem. Biophys. Res. Commun. 401, 306–312 (2010)

    CAS  PubMed  Google Scholar 

  193. C. Bret, D. Hose, T. Reme, A. Kassambara, A. Seckinger, T. Meissner, J.F. Schved, T. Kanouni, H. Goldschmidt, B. Klein, Gene expression profile of ADAMs and ADAMTSs metalloproteinases in normal and malignant plasma cells and in the bone marrow environment. Exp. Hematol. 39, 546–57.e8 (2011)

    CAS  PubMed  Google Scholar 

  194. J. Lin, J. Luo, C. Redies, Differential regional expression of multiple ADAMs during feather bud formation. Dev. Dyn. 240, 2142–2152 (2011)

    CAS  PubMed  Google Scholar 

  195. R. Ma, Z. Tang, K. Sun, X. Ye, H. Cheng, X. Chang, H. Cui, Low levels of ADAM23 expression in epithelial ovarian cancer are associated with poor survival. Pathol. Res. Pract. 214, 1115–1122 (2018)

    CAS  PubMed  Google Scholar 

  196. G. Pampalakis, G. Sotiropoulou, Tissue kallikrein proteolytic cascade pathways in normal physiology and cancer. Biochim. Biophys. Acta 1776, 22–31 (2007)

    CAS  PubMed  Google Scholar 

  197. A. Psyrri, P. Kountourakis, A. Scorilas, S. Markakis, R. Camp, D. Kowalski, E.P. Diamandis, M.A. Dimopoulos, Human tissue kallikrein 7, a novel biomarker for advanced ovarian carcinoma using a novel in situ quantitative method of protein expression. Ann. Oncol. 19, 1271–1277 (2008)

    CAS  PubMed  Google Scholar 

  198. C. Caubet, N. Jonca, M. Brattsand, M. Guerrin, D. Bernard, R. Schmidt, T. Egelrud, M. Simon, G. Serre, Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7. J. Invest. Dermatol. 122, 1235–1244 (2004)

    CAS  PubMed  Google Scholar 

  199. Y. Dong, O.L. Tan, D. Loessner, C. Stephens, C. Walpole, G.M. Boyle, P.G. Parsons, J.A. Clements, Kallikrein-related peptidase 7 promotes multicellular aggregation via the alpha(5)beta(1) integrin pathway and paclitaxel chemoresistance in serous epithelial ovarian carcinoma. Cancer Res. 70, 2624–2633 (2010)

    CAS  PubMed  Google Scholar 

  200. Y. Cui, Y. Wang, H. Li, Q. Li, Y. Yu, X. Xu, B. Xu, T. Liu, Asparaginyl endopeptidase promotes the invasion and metastasis of gastric cancer through modulating epithelial-to-mesenchymal transition and analysis of their phosphorylation signaling pathways. Oncotarget 7, 34356–34370 (2016)

    PubMed  PubMed Central  Google Scholar 

  201. P. Guo, Z. Zhu, Z. Sun, Z. Wang, X. Zheng, H. Xu, Expression of legumain correlates with prognosis and metastasis in gastric carcinoma. PLoS One 8, e73090 (2013)

    CAS  PubMed  PubMed Central  Google Scholar 

  202. Y. Lin, Y. Qiu, C. Xu, Q. Liu, B. Peng, G.F. Kaufmann, X. Chen, B. Lan, C. Wei, D. Lu, Y. Zhang, Y. Guo, Z. Lu, B. Jiang, T.S. Edgington, F. Guo, Functional role of asparaginyl endopeptidase ubiquitination by TRAF6 in tumor invasion and metastasis. J. Natl. Cancer Inst. 106, dju012 (2014)

    PubMed  Google Scholar 

  203. M.H. Haugen, K. Boye, J.M. Nesland, S.J. Pettersen, E.V. Egeland, T. Tamhane, K. Brix, G.M. Maelandsmo, K. Flatmark, High expression of the cysteine proteinase legumain in colorectal cancer - implications for therapeutic targeting. Eur. J. Cancer 51, 9–17 (2015)

    CAS  PubMed  Google Scholar 

  204. Q. Zhu, M. Tang, X. Wang, The expression of asparaginyl endopeptidase promotes growth potential in epithelial ovarian cancer. Cancer Biol. Ther. 18, 222–228 (2017)

  205. J. Cheng, M. Su, Y. Jin, Q. Xi, Y. Deng, J. Chen, W. Wang, Y. Chen, L. Chen, N. Shi, G. Mao, Upregulation of SENP3/SMT3IP1 promotes epithelial ovarian cancer progression and forecasts poor prognosis. Tumour Biol. 39, 1010428317694543 (2017)

    PubMed  Google Scholar 

  206. Y. Klymenko, O. Kim, E. Loughran, J. Yang, R. Lombard, M. Alber, M.S. Stack, Cadherin composition and multicellular aggregate invasion in organotypic models of epithelial ovarian cancer intraperitoneal metastasis. Oncogene 36, 5840–5851 (2017)

    CAS  PubMed  PubMed Central  Google Scholar 

  207. V. Azimian-Zavareh, G. Hossein, M. Ebrahimi, Z. Dehghani-Ghobadi, Wnt11 alters integrin and cadherin expression by ovarian cancer spheroids and inhibits tumorigenesis and metastasis. Exp. Cell Res. 369, 90–104 (2018)

    CAS  PubMed  Google Scholar 

  208. X. Li, M. Tang, Q. Zhu, X. Wang, Y. Lin, X. Wang. The exosomal integrin α5β1/AEP complex derived from epithelial ovarian cancer cells promotes peritoneal metastasis through regulating mesothelial cell proliferation and migration. Cell. Oncol. 43, 263-277 (2020)

  209. C.H. Chen, S.H. Wang, C.H. Liu, Y.L. Wu, W.J. Wang, J. Huang, J.S. Hung, I.R. Lai, J.T. Liang, M.C. Huang, beta-1,4-Galactosyltransferase III suppresses beta1 integrin-mediated invasive phenotypes and negatively correlates with metastasis in colorectal cancer. Carcinogenesis 35, 1258–1266 (2014)

    PubMed  Google Scholar 

  210. Q. Li, S. Liu, B. Lin, L. Yan, Y. Wang, C. Wang, S. Zhang, Expression and correlation of Lewis y antigen and integrins alpha5 and beta1 in ovarian serous and mucinous carcinoma. Int. J. Gynecol. Cancer 20, 1482–1489 (2010)

    CAS  PubMed  Google Scholar 

  211. J.K. Slack-Davis, K.A. Atkins, C. Harrer, E.D. Hershey, M. Conaway, Vascular cell adhesion molecule-1 is a regulator of ovarian cancer peritoneal metastasis. Cancer Res. 69, 1469–1476 (2009)

    CAS  PubMed  Google Scholar 

  212. W.M. Hsu, M.I. Che, Y.F. Liao, H.H. Chang, C.H. Chen, Y.M. Huang, Y.M. Jeng, J. Huang, M.J. Quon, H. Lee, H.C. Huang, M.C. Huang, B4GALNT3 expression predicts a favorable prognosis and suppresses cell migration and invasion via beta(1) integrin signaling in neuroblastoma. Am. J. Pathol. 179, 1394–1404 (2011)

    CAS  PubMed  PubMed Central  Google Scholar 

  213. C.H. Chen, S.W. Wang, C.W. Chen, M.R. Huang, J.S. Hung, H.C. Huang, H.H. Lin, R.J. Chen, M.K. Shyu, M.C. Huang, MUC20 overexpression predicts poor prognosis and enhances EGF-induced malignant phenotypes via activation of the EGFR-STAT3 pathway in endometrial cancer. Gynecol. Oncol. 128, 560–567 (2013)

    CAS  PubMed  Google Scholar 

  214. C.H. Chou, M.J. Huang, C.H. Chen, M.K. Shyu, J. Huang, J.S. Hung, C.S. Huang, M.C. Huang, Up-regulation of C1GALT1 promotes breast cancer cell growth through MUC1-C signaling pathway. Oncotarget 6, 6123–6135 (2015)

    PubMed  PubMed Central  Google Scholar 

  215. M. Yousefi, S. Dehghani, R. Nosrati, H. Zare, M. Evazalipour, J. Mosafer, B.S. Tehrani, A. Pasdar, A. Mokhtarzadeh, M. Ramezani, Aptasensors as a new sensing technology developed for the detection of MUC1 mucin: A review. Biosens. Bioelectron. 130, 1–19 (2019)

    CAS  PubMed  Google Scholar 

  216. Y.F. He, M.Y. Zhang, X. Wu, X.J. Sun, T. Xu, Q.Z. He, W. Di, High MUC2 expression in ovarian cancer is inversely associated with the M1/M2 ratio of tumor-associated macrophages and patient survival time. PLoS One 8, e79769 (2013)

    PubMed  PubMed Central  Google Scholar 

  217. M.P. Ponnusamy, I. Lakshmanan, M. Jain, S. Das, S. Chakraborty, P. Dey, S.K. Batra, MUC4 mucin-induced epithelial to mesenchymal transition: a novel mechanism for metastasis of human ovarian cancer cells. Oncogene 29, 5741–5754 (2010)

    CAS  PubMed  PubMed Central  Google Scholar 

  218. C.H. Chen, M.K. Shyu, S.W. Wang, C.H. Chou, M.J. Huang, T.C. Lin, S.T. Chen, H.H. Lin, M.C. Huang, MUC20 promotes aggressive phenotypes of epithelial ovarian cancer cells via activation of the integrin beta1 pathway. Gynecol. Oncol. 140, 131–137 (2016)

    CAS  PubMed  Google Scholar 

  219. T. Motohara, K. Masuda, M. Morotti, Y. Zheng, S. El-Sahhar, K.Y. Chong, N. Wietek, A. Alsaadi, M. Karaminejadranjbar, Z. Hu, M. Artibani, L.S. Gonzalez, H. Katabuchi, H. Saya, A.A. Ahmed, An evolving story of the metastatic voyage of ovarian cancer cells: cellular and molecular orchestration of the adipose-rich metastatic microenvironment. Oncogene 38, 2885–2898 (2019)

    CAS  PubMed  Google Scholar 

  220. R.L. Anderson, T. Balasas, J. Callaghan, R.C. Coombes, J. Evans, J.A. Hall, S. Kinrade, D. Jones, P.S. Jones, R. Jones, J.F. M+*arshall, M.B. Panico, J.A. Shaw, P.S. Steeg, M. Sullivan, W. Tong, A.D. Westwell, J.W.A. Ritchie, U. K. on behalf of the Cancer Research, C. R. C. A. M. W. G. Cancer Therapeutics, A framework for the development of effective anti-metastatic agents. Nature Rev. Clin. Oncol. 16, 185–204 (2019)

    Google Scholar 

  221. U.H. Weidle, F. Birzele, G. Kollmorgen, R. Rueger, Mechanisms and targets involved in dissemination of ovarian cancer. Cancer Genomics-Proteomics 13, 407–423 (2016)

    CAS  PubMed  Google Scholar 

  222. M.H. Vetter, J.L. Hays, Use of targeted therapeutics in epithelial ovarian cancer: a review of current literature and future directions. Clin. Ther. 40, 361–371 (2018)

    CAS  PubMed  Google Scholar 

  223. B.A. Jones, S. Varambally, R.C. Arend, Histone methyltransferase EZH2: a therapeutic target for ovarian Cancer. Mol. Cancer Ther. 17, 591–602 (2018)

    CAS  PubMed  PubMed Central  Google Scholar 

  224. A. F. Chambers, I. C. MacDonald, E. E. Schmidt, V. L. Morris, A. C. Groom. Clinical targets for anti-metastasis therapy. Adv. Cancer Res. 79, 91-121. (2000)

  225. J.O. van Baal, C.J. van Noorden, R. Nieuwland, K.K. Van de Vijver, A. Sturk, W.J. van Driel, G.G. Kenter, C.A. Lok, Development of peritoneal carcinomatosis in epithelial ovarian cancer: a review. J. Histochem. Cytochem. 66, 67–83 (2018)

    PubMed  Google Scholar 

  226. G.-T. Park, K.-C. Choi, Advanced new strategies for metastatic cancer treatment by therapeutic stem cells and oncolytic virotherapy. Oncotarget 7, 58684 (2016)

    PubMed  PubMed Central  Google Scholar 

  227. V. Conteduca, B. Kopf, S.L. Burgio, E. Bianchi, D. Amadori, U. De Giorgi, The emerging role of anti-angiogenic therapy in ovarian cancer. Int. J. Oncol. 44, 1417–1424 (2014)

    CAS  PubMed  Google Scholar 

  228. M. Barbolina, Molecular Mechanisms Regulating Organ-Specific Metastases in Epithelial Ovarian Carcinoma. Cancers 10, 444 (2018)

    CAS  PubMed Central  Google Scholar 

  229. Á. Áyen, Y. Jimenez Martinez, J. Marchal, H. Boulaiz, Recent Progress in gene therapy for ovarian Cancer. Int. J. Mol. Sci. 19, 1930 (2018)

    PubMed Central  Google Scholar 

  230. X. Chen, L. S. Mangala, L. Mooberry, E. Bayraktar, S. K. Dasari, S. Ma, C. Ivan, K. A. Court, C. Rodriguez-Aguayo, R. Bayraktar. Identifying and targeting angiogenesis-related microRNAs in ovarian cancer. Oncogene 38, 6095-61081 (2019)

  231. U.H. Weidle, F. Birzele, G. Kollmorgen, A. Nopora, Potential microRNA-related targets for therapeutic intervention with ovarian cancer metastasis. Cancer Genomics-Proteomics 15, 1–15 (2018)

    CAS  PubMed  Google Scholar 

  232. B. Wang, X. Li, G. Zhao, H. Yan, P. Dong, H. Watari, M. Sims, W. Li, L.M. Pfeffer, Y. Guo, miR-203 inhibits ovarian tumor metastasis by targeting BIRC5 and attenuating the TGFβ pathway. J. Exp. Clin. Cancer Res. 37, 235 (2018)

    PubMed  PubMed Central  Google Scholar 

  233. X. Zhou, Y. Hu, L. Dai, Y. Wang, J. Zhou, W. Wang, W. Di, L. Qiu. MicroRNA-7 inhibits tumor metastasis and reverses epithelial-mesenchymal transition through AKT/ERK1/2 inactivation by targeting EGFR in epithelial ovarian cancer. PLoS One 9, (2014)

  234. M. Lee, E.J. Kim, Y. Cho, S. Kim, H.H. Chung, N.H. Park, Y.-S. Song, Predictive value of circulating tumor cells (CTCs) captured by microfluidic device in patients with epithelial ovarian cancer. Gynecol. Oncol. 145, 361–365 (2017)

    PubMed  Google Scholar 

  235. T. Fan, Q. Zhao, J.J. Chen, W.T. Chen, M.L. Pearl, Clinical significance of circulating tumor cells detected by an invasion assay in peripheral blood of patients with ovarian cancer. Gynecol. Oncol. 112, 185–191 (2009)

    CAS  PubMed  Google Scholar 

  236. A. Poveda, S.B. Kaye, R. McCormack, S. Wang, T. Parekh, D. Ricci, C.A. Lebedinsky, J.C. Tercero, P. Zintl, B.J. Monk, Circulating tumor cells predict progression free survival and overall survival in patients with relapsed/recurrent advanced ovarian cancer. Gynecol. Oncol. 122, 567–572 (2011)

    PubMed  Google Scholar 

  237. J.D. Kuhlmann, P. Wimberger, A. Bankfalvi, T. Keller, S. Schöler, B. Aktas, P. Buderath, S. Hauch, F. Otterbach, R. Kimmig, S. Kasimir-Bauer, <em>ERCC1</em>-Positive circulating tumor cells in the blood of ovarian cancer patients as a predictive biomarker for platinum resistance. Clin. Chem. 60, 1282–1289 (2014)

    CAS  PubMed  Google Scholar 

  238. M.L. Pearl, Q. Zhao, J. Yang, H. Dong, S. Tulley, Q. Zhang, M. Golightly, S. Zucker, W.T. Chen, Prognostic analysis of invasive circulating tumor cells (iCTCs) in epithelial ovarian cancer. Gynecol. Oncol. 134, 581–590 (2014)

    PubMed  PubMed Central  Google Scholar 

  239. G. Gebauer, M.J. Banys-Paluchowski, H. Neubauer, N. Krawczyk, A. Kaczerowski, P. Paluchowski, F. Meier-Stiegen, A. Abdel-Kawi, T.N. Fehm, Clinical relevance of circulating tumor cells in ovarian, fallopian tube and peritoneal cancer. J. Clin. Oncol. 35, e17080–e1708e (2017)

    Google Scholar 

  240. X. Zhang, H. Li, X. Yu, S. Li, Z. Lei, C. Li, Q. Zhang, Q. Han, Y. Li, K. Zhang, Y. Wang, C. Liu, Y. Mao, X. Wang, D.M. Irwin, H. Guo, G. Niu, H. Tan, Analysis of circulating tumor cells in ovarian cancer and their clinical value as a biomarker. Cell. Physiol. Biochem. 48, 1983–1994 (2018)

    CAS  PubMed  Google Scholar 

  241. E. Lou, R.I. Vogel, D. Teoh, S. Hoostal, A. Grad, M. Gerber, M. Monu, T. Łukaszewski, J. Deshpande, M.A. Linden, M.A. Geller, Assessment of circulating tumor cells as a predictive biomarker of histology in women with suspected ovarian cancer. Lab. Med. 49, 134–139 (2018)

    PubMed  PubMed Central  Google Scholar 

  242. L. Zuo, W. Niu, A. Li, Isolation of circulating tumor cells of ovarian cancer by transferrin immunolipid magnetic spheres and its preliminary clinical application. Nano LIFE 09, 1940001 (2019)

    CAS  Google Scholar 

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Acknowledgments

This study was supported by the Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

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Authors and Affiliations

  1. Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Meysam Yousefi, Mahmoud Ghanei, Arash Salmaninejad & Alireza Pasdar

  2. Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Meysam Yousefi

  3. Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Sadegh Dehghani

  4. Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

    Rahim Nosrati

  5. Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Rahim Nosrati

  6. Halal Research Center of IRI, FDA, Tehran, Iran

    Arash Salmaninejad

  7. Department of Biology, Islamic Azad University, Arsanjan Branch, Arsanjan, Iran

    Sara Rajaie

  8. Department of Gynecologic Oncology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Malihe Hasanzadeh

  9. Bioinformatics Research Group, Mashhad University of Medical Sciences, Mashhad, Iran

    Alireza Pasdar

  10. Division of Applied Medicine, Faculty of Medicine, University of Aberdeen, Foresterhill, Aberdeen, UK

    Alireza Pasdar

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  1. Meysam Yousefi
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Yousefi, M., Dehghani, S., Nosrati, R. et al. Current insights into the metastasis of epithelial ovarian cancer - hopes and hurdles. Cell Oncol. 43, 515–538 (2020). https://doi.org/10.1007/s13402-020-00513-9

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