Malignant invasion of the central nervous system: the hidden face of a poorly understood outcome of prostate cancer

Abstract

Malignancies of the central nervous system include primary brain tumors and brain metastases, the latter being the major cause of intracranial neoplasms in adults. Although prostate cancer (PCa) brain metastases are not the most common source, recent data show that the relevance of prostate cancer brain metastases (PCBM) cannot be neglected. In this review, we focus on the molecular repertory as well as on the phenotypical similarities between PCBM and primary PCa, such as the cellular evolution and the maintenance of androgen-receptor expression. Moreover, the simultaneous occurrence of PCBM with other PCa metastatic sites and the significance of the clinical heterogeneity of the disease are also discussed. In addition, a potential relationship between the heterogeneous behavior exhibited by PCBM and the co-occurrence of malignant cell clusters with distinct genetic profiles is also hypothesized, as well as the prominent role of astrocytes in the establishment of PCBM.

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References

  1. 1.

    Gzell CE, Kench JG, Stockler MR, Hruby G (2013) Biopsy-proven brain metastases from prostate cancer: a series of four cases with review of the literature. Int Urol Nephrol 45:735–742. https://doi.org/10.1007/s11255-013-0462-7

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Humphrey PA (2012) Histological variants of prostatic carcinoma and their significance. Histopathology 60:59–74. https://doi.org/10.1111/j.1365-2559.2011.04039.x

    Article  PubMed  Google Scholar 

  3. 3.

    Hu C-D, Choo R, Huang J (2015) Neuroendocrine differentiation in prostate cancer: a mechanism of radioresistance and treatment failure. Front Oncol 5:1–11. https://doi.org/10.3389/fonc.2015.00090

    Article  Google Scholar 

  4. 4.

    Vinjamoori AH, Jagannathan JP, Shinagare AB et al (2012) Atypical metastases from prostate cancer: 10-year experience at a single institution. Am J Roentgenol 199:367–372. https://doi.org/10.2214/AJR.11.7533

    Article  Google Scholar 

  5. 5.

    Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11–30. https://doi.org/10.3322/caac.21166

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Siegel R, Miller K, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65:29. https://doi.org/10.3322/caac.21254

    Article  Google Scholar 

  7. 7.

    Tremont-Lukats IW, Bobustuc G, Lagos GK et al (2003) Brain metastasis from prostate carcinoma: the M. D. Anderson Cancer Center experience. Cancer 98:363–368. https://doi.org/10.1002/cncr.11522

    Article  PubMed  Google Scholar 

  8. 8.

    Grenader T, Shavit L, Lossos A et al (2007) Brain metastases: a rare initial presentation of prostate cancer. Int Urol Nephrol 39:537–539. https://doi.org/10.1007/s11255-006-9065-x

    Article  PubMed  Google Scholar 

  9. 9.

    Erasmus CE, Verhagen WIM, Wauters CAP, van Lindert EJ (2002) Brain metastasis from prostate small cell carcinoma: not to be neglected. Can J Neurol Sci 29:375–377

    Article  PubMed  Google Scholar 

  10. 10.

    Shou J, Zhang Q, Wang S, Zhang D (2018) The prognosis of different distant metastases pattern in prostate cancer: a population based retrospective study. Prostate. https://doi.org/10.1002/pros.23492

    Article  PubMed  Google Scholar 

  11. 11.

    Watanabe K, Kosaka T, Hongo H et al (2017) Headache caused by brain metastases of castration-resistant prostate cancer during cabazitaxel therapy. Keio J Med 66:65–71. https://doi.org/10.2302/kjm.2016-0014-CR

    Article  PubMed  Google Scholar 

  12. 12.

    Gandaglia G, Karakiewicz PI, Sun M (2014) Beyond the bone: atypical metastases in prostate cancer. Cancer Cell Microenviron. https://doi.org/10.14800/ccm.26

    Article  Google Scholar 

  13. 13.

    Roberts-Thomson R, Rosenthal MA, Gonzales M, Drummond K (2009) Brain metastases in hormone refractory prostate cancer: a changing natural history? Intern Med J 39:205–206. https://doi.org/10.1111/j.1445-5994.2008.01848.x

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Chakraborty PS, Kumar R, Tripathi M et al (2015) Detection of brain metastasis with 68Ga-labeled PSMA ligand PET/CT: a novel radiotracer for imaging of prostate carcinoma. Clin Nucl Med 40:328–329. https://doi.org/10.1097/RLU.0000000000000709

    Article  PubMed  Google Scholar 

  15. 15.

    Hatzoglou V, Patel GV, Morris MJ et al (2014) Brain metastases from prostate cancer: an 11-year analysis in the MRI era with emphasis on imaging characteristics, incidence, and prognosis. J Neuroimaging 24:161–166. https://doi.org/10.1111/j.1552-6569.2012.00767.x

    Article  PubMed  Google Scholar 

  16. 16.

    Calabria FF, Barbarisi M, Gangemi V et al (2018) Molecular imaging of brain tumors with radiolabeled choline PET. Neurosurg Rev 41:67–76. https://doi.org/10.1007/s10143-016-0756-1

    Article  PubMed  Google Scholar 

  17. 17.

    McCutcheon IE, Eng DY, Logothetis CJ (1999) Brain metastasis from prostate carcinoma: antemortem recognition and outcome after treatment. Cancer 86:2301–2311. https://doi.org/10.1002/(sici)1097-0142(19991201)86:11%3c2301::aid-cncr18%3e3.0.co;2-d

  18. 18.

    Alva A, Hussain M (2013) The changing natural history of metastatic prostate cancer. Cancer J 19:19–24. https://doi.org/10.1097/PPO.0b013e318281197e

    Article  PubMed  Google Scholar 

  19. 19.

    Doctor SM, Tsao CK, Godbold JH et al (2014) Is prostate cancer changing?: Evolving patterns of metastatic castration-resistant prostate cancer. Cancer 120:833–839. https://doi.org/10.1002/cncr.28494

    Article  PubMed  Google Scholar 

  20. 20.

    Craig J, Woulfe J, Sinclair J, Malone S (2015) Isolated brain metastases as first site of recurrence in prostate cancer: case report and review of the literature. 22:493–497

    Google Scholar 

  21. 21.

    Barakat T, Agarwal A, McDonald R et al (2016) Solitary brain metastasis from prostate cancer: a case report. Ann Palliat Med 5:402. https://doi.org/10.21037/apm.2016.04.02

    Article  Google Scholar 

  22. 22.

    Lam A, Gan PYC (2017) Metastatic prostate adenocarcinoma to the brain: case reports and literature review. J Neurol Surg Rep 78(1):e62–e65

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Chang J, Kwan B, Panjwani N et al (2017) Prostate adenocarcinoma metastases to the testis and brain: case report and review of the literature. Oxf Med Case Rep 2017:142–144. https://doi.org/10.1093/omcr/omx042

    Article  Google Scholar 

  24. 24.

    Sutton MA, Watkins HL, Green LK, Kadmon D (1996) Intracranial metastases as the first manifestation of prostate cancer. Urology 48:789–793. https://doi.org/10.1016/S0090-4295(96)00238-5

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Mandaliya H, Sung J, Hill J et al (2015) Prostate cancer: cases of rare presentation and rare metastasis. Case Rep Oncol 8:526–529. https://doi.org/10.1159/000442045

    Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Fitzgerald DP, Palmieri D, Hua E et al (2008) Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization. Clin Exp Metastasis 25:799–810. https://doi.org/10.1007/s10585-008-9193-z

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Lorger M, Felding-Habermann B (2010) Capturing changes in the brain microenvironment during initial steps of breast cancer brain metastasis. Am J Pathol 176:2958–2971. https://doi.org/10.2353/ajpath.2010.090838

    Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    O’Brien ER, Kersemans V, Tredwell M et al (2014) Glial activation in the early stages of brain metastasis: TSPO as a diagnostic biomarker. J Nucl Med 55:275–280. https://doi.org/10.2967/jnumed.113.127449

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Wasilewski D, Priego N, Fustero-Torre C, Valiente M (2017) Reactive astrocytes in brain metastasis. Front Oncol 7:1–12. https://doi.org/10.3389/fonc.2017.00298

    Article  Google Scholar 

  30. 30.

    Zhang C, Yu D (2011) Microenvironment determinants of brain metastasis. Cell Biosci 1:8. https://doi.org/10.1186/2045-3701-1-8

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Fokas E, Engenhart-Cabillic R, Daniilidis K et al (2007) Metastasis: the seed and soil theory gains identity. Cancer Metastasis Rev 26:705–715. https://doi.org/10.1007/s10555-007-9088-5

    Article  PubMed  Google Scholar 

  32. 32.

    Palumbo A, de Oliveira Meireles Da Costa N, Bonamino MH et al (2015) Genetic instability in the tumor microenvironment: a new look at an old neighbor. Mol Cancer 14:1–15. https://doi.org/10.1186/s12943-015-0409-y

    CAS  Article  Google Scholar 

  33. 33.

    Langley RR, Fidler IJ (2011) The seed and soil hypothesis revisited—the role of tumor-stroma interactions in metastasis to different organs. Int J Cancer 128:2527–2535. https://doi.org/10.1002/ijc.26031

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Yao D, Dai C, Peng S (2011) Mechanism of the mesenchymal–epithelial transition and its relationship with metastatic tumor formation. Mol Cancer Res 9:1608–1620. https://doi.org/10.1158/1541-7786.MCR-10-0568

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Deryugina EI, Quigley JP (2006) Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 25:9–34. https://doi.org/10.1007/s10555-006-7886-9

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Quail DF, Joyce JA (2013) Microenvironmental regulation of tumor progression and metastasis. Nat Med 19:1423–1437. https://doi.org/10.1038/nm.3394

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Gandaglia G, Abdollah F, Schiffmann J et al (2014) Distribution of metastatic sites in patients with prostate cancer: a population-based analysis. Prostate 74:210–216. https://doi.org/10.1002/pros.22742

    Article  PubMed  Google Scholar 

  38. 38.

    Coulson-Thomas VJ, Gesteira TF, Coulson-Thomas YM et al (2010) Fibroblast and prostate tumor cell cross-talk: fibroblast differentiation, TGF-β, and extracellular matrix down-regulation. Exp Cell Res 316:3207–3226. https://doi.org/10.1016/j.yexcr.2010.08.005

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Thudi NK, Shu ST, Martin CK et al (2011) Development of a brain metastatic canine prostate cancer cell line. Prostate 71:1251–1263. https://doi.org/10.1002/pros.21341

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Pollard ME, Moskowitz AJ, Diefenbach MA, Hall SJ (2017) Cost-effectiveness analysis of treatments for metastatic castration resistant prostate cancer. Asian J Urol 4:37–43. https://doi.org/10.1016/j.ajur.2016.11.005

    Article  PubMed  Google Scholar 

  41. 41.

    Geldof AA (1997) Models for cancer skeletal metastasis: a reappraisal of Batson’s plexus. Anticancer Res 17:1535–1539

    CAS  PubMed  Google Scholar 

  42. 42.

    Bubendorf L, Schöpfer A, Wagner U et al (2000) Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol 31:578–583. https://doi.org/10.1053/hp.2000.6698

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Arya M, Bott SR, Shergill IS et al (2006) The metastatic cascade in prostate cancer. Surg Oncol 15:117–128. https://doi.org/10.1016/j.suronc.2006.10.002

    Article  PubMed  Google Scholar 

  44. 44.

    Benjamin R (2002) Neurologic complications of prostate cancer. Am Fam Physician 65:1834–1840

    PubMed  Google Scholar 

  45. 45.

    Nathoo N, Caris EC, Wiener JA, Mendel E (2011) History of the vertebral venous plexus and the significant contributions of breschet and batson. Neurosurgery 69:1007–1014. https://doi.org/10.1227/NEU.0b013e3182274865

    Article  PubMed  Google Scholar 

  46. 46.

    Batson O (1940) The function of the vertebral veins and their role in the spread of metastases. Ann Surg 112:138–149

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Ehninger A, Trumpp A (2011) The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in. J Exp Med 208(3):421–428. https://doi.org/10.1084/jem.20110132

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Nishijima J, Koiso K, Nemoto R (1995) The role of the vertebral veins in the dissemination of prostate carcinoma. Jpn J Urol 86:927–932. https://doi.org/10.1016/S0022-5347(17)54735-7

    CAS  Article  Google Scholar 

  49. 49.

    Morgan JWM, Adcock KA, Donohue RE (1990) Distribution of skeletal metastases in prostatic and lung cancer. Mechanisms of skeletal metastases. Urology 36:31–34. https://doi.org/10.1016/0090-4295(90)80308-A

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    Chiang P-H, Lee T-C, Huang C-C (2004) Intracranial metastasis of prostate cancer: report of two cases. Chang Gung Med J 27:770–776

    PubMed  Google Scholar 

  51. 51.

    Olson KB, Pienta KJ (2006) Prostate cancer presenting as visual changes. Anticancer Res 26:755–758

    PubMed  Google Scholar 

  52. 52.

    Guedes BDVS, Da Rocha AJ, Gama HPP, Da Silva CJ (2011) Dural metastases from prostate carcinoma: a systematic review of the literature apropos of six patients. Eur J Radiol 80:236–240. https://doi.org/10.1016/j.ejrad.2010.06.007

    Article  Google Scholar 

  53. 53.

    Scarrow AM, Rajendran PR, Marion D (2000) Metastatic prostate adenocarcinoma of the dura mater. Br J Neurosurg 14:473–474

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Penley MW, Kim YC, Pribram HFW (1981) Subdural metastases from prostatic adenocarcinoma. Surg Neurol 16:131–134. https://doi.org/10.1016/0090-3019(81)90114-2

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Confavreux CBN, Cotton F, Tebib JG (2006) Advanced MRI could help to differentiate meningeal carcinomatosis with mass effect from cerebral metastasis in prostate cancer. Bull Cancer 93(4):E31–35

    PubMed  Google Scholar 

  56. 56.

    Wasserstrom WR, Glass JP, Posner JB (1982) Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer 49:759–72. https://doi.org/10.1002/1097-0142(19820215)49:4%3c759::aid-cncr2820490427%3e3.0.co;2-7

  57. 57.

    Lin C, Turner S, Gurney H, Peduto A (2008) Increased detections of leptomeningeal presentations in men with hormone refractory prostate cancer: an effect of improved systemic therapy? J Med Imaging Radiat Oncol 52:376–381. https://doi.org/10.1111/j.1440-1673.2008.01973.x

    CAS  Article  PubMed  Google Scholar 

  58. 58.

    Orphanos G, Ardavanis A (2010) Leptomeningeal metastases from prostate cancer: an emerging clinical conundrum. Clin Exp Metastasis 27:19–23. https://doi.org/10.1007/s10585-009-9298-z

    Article  PubMed  Google Scholar 

  59. 59.

    Izumi K, Mizokami A, Narimoto K et al (2010) Cranial nerve deficit caused by skull metastasis of prostate cancer: three Japanese castration-resistant prostate cancer cases. Int J Clin Oncol 15:631–634. https://doi.org/10.1007/s10147-010-0098-x

    Article  PubMed  Google Scholar 

  60. 60.

    Deinsberger R, Regatschnig R, Kaiser B, Bankl HC (2006) Spinal leptomeningeal metastases from prostate cancer. Acta Neurochir (Wien) 148:467–471. https://doi.org/10.1007/s00701-005-0687-z

    CAS  Article  Google Scholar 

  61. 61.

    Preusser M, Capper D, Ilhan-Mutlu A et al (2012) Brain metastases: pathobiology and emerging targeted therapies. Acta Neuropathol 123:205–222. https://doi.org/10.1007/s00401-011-0933-9

    CAS  Article  PubMed  Google Scholar 

  62. 62.

    Vandenhaute E, Stump-Guthier C, Losada ML et al (2015) The choroid plexus may be an underestimated site of tumor invasion to the brain: an in vitro study using neuroblastoma cell lines. Cancer Cell Int 15:1–8. https://doi.org/10.1186/s12935-015-0257-2

    CAS  Article  Google Scholar 

  63. 63.

    Strazielle N, Ghersi-Egea JF (2013) Physiology of blood–brain interfaces in relation to brain disposition of small compounds and macromolecules. Mol Pharm 10:1473–1491. https://doi.org/10.1021/mp300518e

    CAS  Article  Google Scholar 

  64. 64.

    Nabavizadeh SA, Feygin T, Harding BN et al (2014) Imaging findings of patients with metastatic neuroblastoma to the brain. Acad Radiol 21:329–337. https://doi.org/10.1016/j.acra.2013.10.016

    Article  PubMed  Google Scholar 

  65. 65.

    Codreanu I, Dasanu CA, Zhuang H (2014) Neuroblastoma with a solitary intraventricular brain metastasis visualized on I-123 MIBG scan. J Neuroimaging 24:202–204. https://doi.org/10.1111/j.1552-6569.2012.00754.x

    Article  PubMed  Google Scholar 

  66. 66.

    Suki D, Khoury Abdulla R, Ding M et al (2014) Brain metastases in patients diagnosed with a solid primary cancer during childhood: experience from a single referral cancer center. J Neurosurg Pediatr 14:372–385. https://doi.org/10.3171/2014.7.peds13318

    Article  PubMed  Google Scholar 

  67. 67.

    Shapira Y, Hadelsberg UP, Kanner AA et al (2014) The ventricular system and choroid plexus as a primary site for renal cell carcinoma metastasis. Acta Neurochir (Wien) 156:1469–1474. https://doi.org/10.1007/s00701-014-2108-7

    Article  Google Scholar 

  68. 68.

    Siomin V, Lin JL, Marko NF et al (2011) Stereotactic radiosurgical treatment of brain metastases to the choroid plexus. Int J Radiat Oncol Biol Phys 80:1134–1142. https://doi.org/10.1016/j.ijrobp.2010.03.016

    Article  PubMed  Google Scholar 

  69. 69.

    Sharifi G, Bakhtevari MH, Alghasi M et al (2015) Bilateral choroid plexus metastasis from papillary thyroid carcinoma: case report and review of the literature. World Neurosurg 84:1142–1146. https://doi.org/10.1016/j.wneu.2015.05.027

    Article  PubMed  Google Scholar 

  70. 70.

    Platz EA, Giovannucci E (2004) The epidemiology of sex steroid hormones and their signaling and metabolic pathways in the etiology of prostate cancer. J Steroid Biochem Mol Biol 92:237–253. https://doi.org/10.1016/j.jsbmb.2004.10.002

    CAS  Article  PubMed  Google Scholar 

  71. 71.

    Bailey KC, Funaro K, Aguila S et al (2014) A case of intraventricular primary central nervous system lymphoma. J Radiol Case Rep 8:1–8. https://doi.org/10.3941/jrcr.v8i3.1361

    Article  PubMed  PubMed Central  Google Scholar 

  72. 72.

    Patchell RA (2003) The management of brain metastases. Cancer Treat Rev 29:533–540. https://doi.org/10.1016/S0305-7372(03)00105-1

    Article  PubMed  Google Scholar 

  73. 73.

    Norden AD, Wen PYKS (2005) Brain metastases. Curr Opin Neurol 18:654–661

    PubMed  Google Scholar 

  74. 74.

    Eichler AF, Chung E, Kodack DP et al (2011) The biology of brain metastases—translation to new therapies. Nat Rev Clin Oncol 8:344–356. https://doi.org/10.1038/nrclinonc.2011.58

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  75. 75.

    Stone KR, Mickey DD, Wunderli H et al (1978) Isolation of a human prostate carcinoma cell line (DU 145). Int J Cancer 21:274–281. https://doi.org/10.1002/ijc.2910210305

    CAS  Article  PubMed  Google Scholar 

  76. 76.

    Martin V, Cuenca X, Lopez S et al (2015) Iris metastasis from prostate carcinoma: a case report and review of the literature. Cancer Radiother 19:331–333. https://doi.org/10.1016/j.canrad.2014.12.008

    CAS  Article  PubMed  Google Scholar 

  77. 77.

    Hutton R, Maguire J, Amer T et al (2015) Intracranial metastasis of adenocarcinoma of the prostate presenting with symptoms of spinal cord compression. Indian J Surg 77:75–76. https://doi.org/10.1007/s12262-014-1143-1

    Article  PubMed  Google Scholar 

  78. 78.

    Witkowska-Patena E, Gizewska A, Stembrowicz-Nowakowska Z et al (2015) Brain metastases in patient with prostate cancer found in 18F-choline PET/CT. Nucl Med Rev Nucl Med Rev 18:39–41. https://doi.org/10.5603/NMR.2015.0010

    Article  Google Scholar 

  79. 79.

    Chan M, Hsiao E, Turner J (2017) Cerebellar metastases from prostate cancer on 68Ga-PSMA PET/CT. Clin Nucl Med 42:193–194. https://doi.org/10.1097/RLU.0000000000001526

    Article  PubMed  Google Scholar 

  80. 80.

    Wei X, Schlenkhoff C, Schwarz B et al (2017) Combination of 177Lu-PSMA-617 and external radiotherapy for the treatment of cerebral metastases in patients with castration-resistant metastatic prostate cancer. Clin Nucl Med 42:704–706. https://doi.org/10.1097/RLU.0000000000001763

    Article  PubMed  Google Scholar 

  81. 81.

    Dureja S, Thakral P, Pant V, Sen I (2017) Rare sites of metastases in prostate cancer detected on Ga-68 PSMA PET/CT scan-a case series. Indian J Nucl Med 32:13. https://doi.org/10.4103/0972-3919.198450

    Article  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Flannery T, Kano H, Niranjan A et al (2010) Stereotactic radiosurgery as a therapeutic strategy for intracranial metastatic prostate carcinoma. J Neurooncol 96:369–374. https://doi.org/10.1007/s11060-009-9966-5

    Article  PubMed  Google Scholar 

  83. 83.

    Hobisch A, Culig Z, Radmayr C et al (1995) Distant metastases from prostatic carcinoma express androgen receptor protein. Cancer Res 55:3068–3072

    CAS  PubMed  Google Scholar 

  84. 84.

    Antonarakis ES, Armstrong AJ, Dehm SM, Luo J (2016) Androgen receptor variant-driven prostate cancer: clinical implications and therapeutic targeting. Prostate Cancer Prostatic Dis 19:231–241. https://doi.org/10.1038/pcan.2016.17

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Abeshouse A, Ahn J, Akbani R et al (2015) The molecular taxonomy of primary prostate cancer. Cell 163:1011–1025. https://doi.org/10.1016/j.cell.2015.10.025

    CAS  Article  Google Scholar 

  86. 86.

    Grigore AD, Ben-Jacob E, Farach-Carson MC (2015) Prostate cancer and neuroendocrine differentiation: more neuronal, less endocrine? Front Oncol 5:1–19. https://doi.org/10.3389/fonc.2015.00037

    Article  Google Scholar 

  87. 87.

    Marcu M, Radu E, Sajin M (2010) Neuroendocrine transdifferentiation of prostate carcinoma cells and its prognostic significance. Rom J Morphol Embryol 51:7–12

    PubMed  Google Scholar 

  88. 88.

    Vashchenko N, Abrahamsson P (2005) Neuroendocrine differentiation in prostate cancer: implications for new treatment modalities. Eur Urol 47:147–155. https://doi.org/10.1016/j.eururo.2004.09.007

    CAS  Article  PubMed  Google Scholar 

  89. 89.

    Li Q, Zhang CS, Zhang Y (2016) Molecular aspects of prostate cancer with neuroendocrine differentiation. Chin J Cancer Res 28:122–129. https://doi.org/10.3978/j.issn.1000-9604.2016.01.02

    Article  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Bonkhoff H (2001) Neuroendocrine differentiation in human prostate cancer. Morphogenesis, proliferation and androgen receptor status. Ann Oncol 12(Suppl 2):S141–S144

    Article  PubMed  Google Scholar 

  91. 91.

    Epstein JI, Amin MB, Beltran H et al (2014) Proposed morphologic classification of prostate cancer with neuroendocrine differentiation. Am J Surg Pathol 38:756–767. https://doi.org/10.1109/TMI.2012.2196707.Separate

    Article  PubMed  PubMed Central  Google Scholar 

  92. 92.

    Evans AJ, Humphrey PA, Belani J et al (2006) Large cell neuroendocrine carcinoma of prostate: a clinicopathologic summary of 7 cases of a rare manifestation of advanced prostate cancer. Am J Surg Pathol 30:684–693

    Article  PubMed  Google Scholar 

  93. 93.

    Hobisch A, Culig Z, Radmayr C et al (1995) Distant metastases from prostatic carcinoma express androgen receptor protein distant metastases from prostatic carcinoma express androgen receptor protein 1:3068–3072

    Google Scholar 

  94. 94.

    Gerlinger M, Rowan AJ, Horswell S et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366:883–892. https://doi.org/10.1056/NEJMoa1113205

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  95. 95.

    Armstrong AJ, Garrett-Mayer ES, Yang YCO et al (2007) A contemporary prognostic nomogram for men with hormone-refractory metastatic prostate cancer: a TAX327 study analysis. Clin Cancer Res 13:6396–6403. https://doi.org/10.1158/1078-0432.CCR-07-1036

    CAS  Article  PubMed  Google Scholar 

  96. 96.

    Pouessel D, Gallet B, Bibeau F et al (2007) Liver metastases in prostate carcinoma: clinical characteristics and outcome. BJU Int 99:807–811. https://doi.org/10.1111/j.1464-410X.2006.06663.x

    CAS  Article  PubMed  Google Scholar 

  97. 97.

    Gundem G, Van Loo P, Kremeyer B, Alexandrov LB, Tubio JMC, Papaemmanuil E, Brewer DS, Kallio HML, Hӧgnäs G, Annala M, Kivinummi K, Goody V, Latimer C, O’Meara S, Dawson KJ, Isaacs W, Emmert-Buck MR et al (2015) The evolutionary history of lethal metastatic prostate cancer. Nature. https://doi.org/10.1038/nature14347.the (in press)

    Article  PubMed  PubMed Central  Google Scholar 

  98. 98.

    Hansson J, Abrahamsson P-A (2003) Neuroendocrine differentiation in prostatic carcinoma. Scand J Urol Nephrol Suppl 148:28–36. https://doi.org/10.1016/S0046-8177(87)80060-6

    Article  Google Scholar 

  99. 99.

    Chandrasekar T, Yang JC, Gao AC, Evans CP (2015) Mechanisms of resistance in castration-resistant prostate cancer (CRPC). Transl Androl Urol 4:365–380. https://doi.org/10.3978/j.issn.2223-4683.2015.05.02

    Article  PubMed  PubMed Central  Google Scholar 

  100. 100.

    Zejnullahu K, Arevalo MG, Ryan CJ, Aggarwal R (2016) Approaches to minimize castration in the treatment of advanced prostate cancer. Urol Oncol 34(8):368–374. https://doi.org/10.1016/j.urolonc.2016.02.001

    Article  PubMed  Google Scholar 

  101. 101.

    Katzenwadel A, Wolf P (2015) Androgen deprivation of prostate cancer: leading to a therapeutic dead end. Cancer Lett 367:12–17. https://doi.org/10.1016/j.canlet.2015.06.021

    CAS  Article  PubMed  Google Scholar 

  102. 102.

    Magnan S, Zarychanski R, Pilote L et al (2015) Intermittent vs continuous androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis. JAMA Oncol 1:1261–1269. https://doi.org/10.1001/jamaoncol.2015.2895

    Article  PubMed  Google Scholar 

  103. 103.

    Schroeder A, Herrmann A, Cherryholmes G et al (2014) Loss of androgen receptor expression promotes a stem-like cell phenotype in prostate cancer through STAT3 signaling. Cancer Res 74:1227–1237. https://doi.org/10.1158/0008-5472.CAN-13-0594

    CAS  Article  PubMed  Google Scholar 

  104. 104.

    Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141:52–67. https://doi.org/10.1016/j.cell.2010.03.015

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  105. 105.

    Rakic P (2003) Elusive radial glial cells: historical and evolutionary perspective. Glia 43:19–32. https://doi.org/10.1002/glia.10244

    Article  PubMed  Google Scholar 

  106. 106.

    Verkhratsky A, Steinhauser C (2000) Ion channels in glial cells. Brain Res Rev 32:380–412

    CAS  Article  PubMed  Google Scholar 

  107. 107.

    Seifert G, Schilling K, Steinhäuser C (2006) Astrocyte dysfunction in neurological disorders: a molecular perspective. Nat Rev Neurosci 7:194–206. https://doi.org/10.1038/nrn1870

    CAS  Article  PubMed  Google Scholar 

  108. 108.

    Gonzalez-Perez O, Lopez-Virgen V, Quiñones-Hinojosa A (2015) Astrocytes: everything but the glue. Neuroimmunol Neuroinflamm 2:115–117. https://doi.org/10.4103/2347-8659.153979

    Article  PubMed  PubMed Central  Google Scholar 

  109. 109.

    Yang CZ, Zhao R, Dong Y et al (2008) Astrocyte and neuron intone through glutamate. Neurochem Res 33:2480–2486. https://doi.org/10.1007/s11064-008-9758-x

    CAS  Article  PubMed  Google Scholar 

  110. 110.

    Abbott NJ, Patabendige AAK, Dolman DEM et al (2010) Structure and function of the blood–brain barrier. Neurobiol Dis 37:13–25. https://doi.org/10.1016/j.nbd.2009.07.030

    CAS  Article  PubMed  Google Scholar 

  111. 111.

    Crooks DA, Scholtz CL, Vowles G et al (1991) The glial reaction in closed head injuries. Neuropathol Appl Neurobiol 17:407–414

    CAS  Article  PubMed  Google Scholar 

  112. 112.

    Ridet JL, Malhotra SK, Privat A, Gage FH (1997) Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci 20:570–577. https://doi.org/10.1016/S0166-2236(97)01139-9

    CAS  Article  PubMed  Google Scholar 

  113. 113.

    Lee SJ, Benveniste EN (1999) Adhesion molecule expression and regulation on cells of the central nervous system. J Neuroimmunol 98:77–88

    CAS  Article  PubMed  Google Scholar 

  114. 114.

    Taylor AR, Robinson MB, Gifondorwa DJ et al (2007) Regulation of heat shock protein 70 release in astrocytes: role of signaling kinases. Dev Neurobiol 67:1815–1829. https://doi.org/10.1002/dneu.20559

    CAS  Article  PubMed  Google Scholar 

  115. 115.

    Araque A (2006) Astrocyte-neuron signaling in the brain—implications for disease. Curr Opin Investig Drugs 7:619–624

    CAS  PubMed  Google Scholar 

  116. 116.

    Chen Q, Boire A, Jin X et al (2016) Carcinoma–astrocyte gap junctions promote brain metastasis by cGAMP transfer. Nature 533:493–498. https://doi.org/10.1038/nature18268

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  117. 117.

    Lin Q, Balasubramanian K, Fan D et al (2010) Reactive astrocytes protect melanoma ells from chemotherapy by sequestering intracellular calcium through gap junction communication channels. Neoplasia 12:748–754. https://doi.org/10.1593/neo.10602

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  118. 118.

    Kim S-J, Kim J-S, Park ES et al (2011) Astrocytes upregulate survival genes in tumor cells and induce protection from chemotherapy. Neoplasia 13:286–298. https://doi.org/10.1158/1538-7445.AM10-3428

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  119. 119.

    Xing F, Kobayashi A, Okuda H et al (2013) Reactive astrocytes promote the metastatic growth of breast cancer stem-like cells by activating Notch signalling in brain. EMBO Mol Med 5:384–396. https://doi.org/10.1002/emmm.201201623

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  120. 120.

    Dai W, Zhu H, Chen G et al (2016) Orchestration of the crosstalk between astrocytes and cancer cells affects the treatment and prognosis of lung cancer sufferers with brain metastasis. J Thorac Dis 8:E1450–E1454. https://doi.org/10.21037/jtd.2016.11.11

    Article  PubMed  PubMed Central  Google Scholar 

  121. 121.

    Marchetti D, Li J, Shen R (2000) Astrocytes Contribute to the Brain-metastatic Specificity of Melanoma Cells by Producing Heparanase. Cancer Res 60(17):4767–4770

    CAS  PubMed  Google Scholar 

  122. 122.

    Kaverina N, Borovjagin AV, Kadagidze Z et al (2017) Astrocytes promote progression of breast cancer metastases to the brain via a KISS1-mediated autophagy. Autophagy 13:1905–1923. https://doi.org/10.1080/15548627.2017.1360466

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  123. 123.

    Seike T, Fujita K, Yamakawa Y et al (2011) Interaction between lung cancer cells and astrocytes via specific inflammatory cytokines in the microenvironment of brain metastasis. Clin Exp Metastasis 28:13–25. https://doi.org/10.1007/s10585-010-9354-8

    CAS  Article  PubMed  Google Scholar 

  124. 124.

    Klein A, Schwartz H, Sagi-Assif O et al (2015) Astrocytes facilitate melanoma brain metastasis via secretion of IL-23. J Pathol 236:116–127. https://doi.org/10.1002/path.4509

    CAS  Article  Google Scholar 

  125. 125.

    Wang L, Cossette SM, Rarick KR et al (2013) Astrocytes directly influence tumor cell invasion and metastasis in vivo. PLoS One. https://doi.org/10.1371/journal.pone.0080933

    Article  PubMed  PubMed Central  Google Scholar 

  126. 126.

    de Oliveira Barros EG, Palumbo A, Mello PLP et al (2014) The reciprocal interactions between astrocytes and prostate cancer cells represent an early event associated with brain metastasis. Clin Exp Metastasis. https://doi.org/10.1007/s10585-014-9640-y

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors would like to acknowledge the financial support provided by the following agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa Carlos Chagas Filho (FAPERJ), and Programa de Oncobiologia da Fundação do Cancer Ary Frauzino.

Funding

The financial Grants provided by the following agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Amparo à Pesquisa Carlos Chagas Filho (FAPERJ), and Programa de Oncobiologia da Fundação do Cancer Ary Frauzino supported the scientific activities from the following researchers: Eliane Gouvêa de Oliveira Barros and Antonio Palumbo júnior.

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de Oliveira Barros, E.G., Meireles Da Costa, N., Palmero, C.Y. et al. Malignant invasion of the central nervous system: the hidden face of a poorly understood outcome of prostate cancer. World J Urol 36, 2009–2019 (2018). https://doi.org/10.1007/s00345-018-2392-6

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Keywords

  • Prostate cancer
  • Brain metastasis
  • Astrocytes
  • Prostate cancer brain metastases
  • Microenvironment