Basal-luminal epithelial cell differentiation in prostate cancer is associated with epithelial-mesenchymal transition and epithelium migration in the mesenchyme


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Abstract

Aim In patients with prostate cancer to trace the pathway of the malignant cells of the basal layer of the prostate epithelium during their differentiation into luminal cells and/or migration in the mesenchyme. Materials and methods We used histological and immunohistochemical staining of the markers of the basal layer of the prostate: cytokeratin 5 (CK5), E-cadherin and AMACR, and Western blot to assess the production of the same markers in epithelial and stromal compartments of malignant and normal prostate tissue in patients with prostate cancer. Results Our findings revealed that prostate cancer is associated with losing of the basal epithelial layer in the prostate tumor tissue, which is accompanied by a complete loss of CK5 secretion, increased levels of E-cadherin and AMACR in luminal epithelium and the emergence of cells producing E-cadherin and AMACR in the stromal compartment of the prostate. Discussion These findings suggest that in prostate cancer the transformation the basal layer of the epithelial cells is associated with their differentiation into luminal cells and migration into the surrounding mesenchyme due to epithelial-mesenchymal transition. Conclusion Prostate cancer pathogenesis of associated with changes in epithelial cell pathways and the levels of the markers’ expression. Their assessment can be used for studying the disease mechanisms and seeking new diagnosis and treatment options.

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About the authors

O. V Korshak

Almazov North-Western Federal Medical Research Centre

Email: olga.korshak@gmail.com

E. N Sushilova

Institute of Cytology RAS

Email: sushilovak@yandex.ru

M. A Voskresenskii

Multidisciplinary City Hospital №2, St.Petersburg

Email: Voskresenskiym@mail.ru

R. V Grozov

Almazov North-Western Federal Medical Research Centre

Email: pathologist78@mail.ru

B. K Komyakov

Multidisciplinary City Hospital №2, St.Petersburg

Email: komyakovbk@mail.ru

A. Y Zarytskey

Almazov North-Western Federal Medical Research Centre

Email: zaritskey@gmail.com

B. V Popov

Institute of Cytology RAS; I.I. Mechnikov North-Western State Medical University

Email: borisvp478@gmaiI.com
D.Sci., Leading Researcher, Institute of Cytology RAS

References

  1. Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin D.M., Forman D., Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer. 2015;136(5):E359-86. doi: 10.1002/ijc.29210.
  2. Howlader N., Noone A.M., Krapcho M. et al. SEER cancer statistics review, 1975-2011 (Vintage 2011 populations). Retrieved from http://www.seer.cancer.gov/csr/2014.
  3. Bashir M.N. Epidemiology of Prostate Cancer. Asian Pac. J. Cancer Prev. 2015; 16(13):5137-5141.
  4. Глыбочко П.В., Аляев Ю.Г., Амосов А.В., Крупинов Г.Е., Обухов А.А., Ганжа Т.М., Новичков Н.Д. Ранняя диагностика рака предстательной железы с помощью гистосканирования. Андрология и генитальная хирургия. 2014;15(2):37-43). D0I:10.17650/2070-9781-2014-2-37-43
  5. Abate-Shen C., Shen M.M. Molecular genetics of prostate cancer. Genes Dev. 2000;14(19):2410-2434.
  6. Bethel C.R., Faith D., Li X., Guan B., Hicks J.L., Lan F., Jenkins R.B., Bieberich C.J., DeMarzo A.M. Decreased NKX3.1 protein expression in focal prostatic atrophy, prostatic intraepithelial neoplasia, and adenocarcinoma: association with gleason score and chromosome 8p deletion. Cancer Res. 2006;66(22):10683-10690.
  7. El-Alfy M., Pelletier G., Hermo L.S., Labrie F. Unique features of the basal cells of human prostate epithelium. Microsc. Res. Tech. 2000;51(5):436-446.
  8. Vashchenko N., Abrahamsson P.A. Neuroendocrine differentiation in prostate cancer: implications for new treatment modalities. Eur. Urol. 2005;47(2):147-155.
  9. Min J., Zaslavsky A., Fedele G., McLaughlin S.K., Reczek E.E., De Raedt T., Guney I., Strochlic D.E., Macconaill L.E., Beroukhim R., Bronson R.T., Ryeom S., Hahn W.C., Loda M., Cichowski K. An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-kappaB. Nat. Med. 2010;16(3):286-294. doi: 10.1038/nm.2100.
  10. Burger P.E., Xiong X., Coetzee S., Salm S.N., Moscatelli D., Goto K., Wilson E.L. Sca-1 expression identifies stem cells in the proximal region of prostatic ducts with high capacity to reconstitute prostatic tissue. Proc. Natl. Acad. Sci. USA. 2005;102(20):7180-7185.
  11. Goldstein A.S., Huang J., Guo C., Garraway I.P., Witte O.N. Identification of a cell of origin for human prostate cancer. Science. 2010;329(5991):568-571. doi: 10.1126/science.1189992.
  12. Tomlins S.A., Rhodes D.R., Perner S., Dhanasekaran S.M., Mehra R., Sun X.W., Varambally S., Cao X., Tchinda J., Kuefer R., Lee C., Montie J.E., Shah R.B., Pienta K.J., Rubin M.A., Chinnaiyan A.M. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005;310(5748): 644-648.
  13. Carver B.S., Tran J., Gopalan A., Chen Z., Shaikh S., Carracedo A., Alimonti A., Nardella C., Varmeh S., Scardino P.T., Cordon-Cardo C., Gerald W., Pandolfi P.P. Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate. Nat. Genet. 2009;41(5):619-624.
  14. Zong Y., Xin L., Goldstein A.S., Lawson D.A., Teitell M.A., Witte O.N. ETS family transcription factors collaborate with alternative signaling pathways to induce carcinoma from adult murine prostate cells. Proc. Natl. Acad. Sci. USA. 2009;106(30):12465-12470. doi: 10.1073/pnas.0905931106.
  15. Reya T., Morrison S.J., Clarke M.F., Weissman I.L. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105-111.
  16. Pardal R., Clarke M.F., Morrison S. J. 2003. Applying the principles of stem-cell biology to cancer. Nat. Rev. Cancer. 2003;3:895-902.
  17. O’Brien C.A., Pollett A., Gallinger S., Dick J.E. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445:106-110.
  18. Thiery J.P., Acloque H., Huang R.Y., Nieto M.A. Epithelialmesenchymal transitions in development and disease. Cell. 2009;139:871-890.
  19. Caramel J., Papadogeorgakis E., Hill L., Browne G.J., Richard G., Wierinckx A., Saldanha G., Osborne J., Hutchinson P., Tse G., Lachuer J., Puisieux A., Pringle J. H., Ansieau S., Tulchinsky E. 2013. A switch in the expression of embryonic EMT-inducers drives the development of malignant melanoma. Cancer Cell. 2009;24:466-480.
  20. Park S.M., Gaur A.B., Lengyel E., Peter M.E. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008;22(7):894-907. doi: 10.1101/gad.1640608.
  21. Xin L. Cells of origin for cancer: an updated view from prostate cancer. Oncogene. 2013;32:3655-3663.
  22. Shibata M., Shen M.M. Stem cells in genetically-engineered mouse models of prostate cancer. Endocr. Relat. Cancer. 2015;22(6):199-208.
  23. Moll R., Divo M., Langbein L. The human keratins: biology and pathology. Histochem. Cell. Biol. 2008;129:705-733.
  24. Long R.M., Morrissey C., Fitzpatrick J.M., Watson R.W. Prostate epithelial cell differentiation and its relevance to the understanding of prostate cancer therapies. Clin. Sci. (Lond). 2005;108:1-11.
  25. Wong A.S., Gumbiner B.M. Adhesion-independent mechanism for suppression of tumor cell invasion by E-cadherin. J. Cell Biol. 2003;161(6):1191-1203.
  26. Tam W.L., Weinberg R.A. The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat. Med. 2013;19:1438-1449.
  27. Herranz N., Pasini D., Diaz V.M., Franci C., Gutierrez A., Dave N., Escrivà M., Hernandez-Munoz I., Di Croce L., Helin K., Garcia de Herreros A., Peirö S. Polycomb complex 2 is required for E-cadherin repression by the Snail1 transcription factor. Mol. Cell. Biol. 2008;28(15):4772-7781.
  28. Yates C. Prostate tumor cell plasticity: a consequence of the microenvironment. Adv. Exp. Med. Biol. 2011;720:81-90.
  29. Onder T.T., Gupta P.B., Mani S.A., Yang J., Lander E.S., Weinberg R.A. Loss ofE-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res. 2008;68(10):3645-3654. doi: 10.1158/0008-5472.CAN-07-2938.
  30. Cao Q., Yu J., Dhanasekaran S.M., Kim J.H., Mani R.S., Tomlins S.A., Mehra R., Laxman B., Cao X., Yu J., Kleer C.G., Varambally S., Chinnaiyan A.M. Repression of E-cadherin by the polycomb group protein EZH2 in cancer. Oncogene. 2008;27(58):7274-7284.
  31. Grant C.M., Kyprianou N. Epithelial mesenchymal transition (EMT) in prostate growth and tumor progression. Transl. Androl. Urol. 2013;2(3):202-211.
  32. Petrov N.S., Voskresensky M.A., Grosov R.V., Korshak O.V., Zaritsky A.Y., Vereschagina N.A., Komyakov B.K., Popov B.V. Markers of the prostate basal layer cells are effective indicators of its malignant transformation. Tsitologiia. 2016;58(7):526-533. Russian (Петров Н.С., Воскресенский М.А., Грозов Р.В., Коршак О.В., Зарицкий А.Ю., Верещагина Н.А., Комяков Б.К., Попов Б.В. Маркеры клеток базального слоя эпителия предстательной железы являются эффективными индикаторами ее злокачественной трансформации. Цитология. 2016; 58(7):526-533).
  33. Maitland N.J., Frame F.M., Polson E.S., Lewis J.L., Collins A.T. Prostate cancer stem cells: do they have a basal or luminal phenotype? Horm. Cancer. 2011;2:47-61.
  34. Humphrey P.A. Diagnosis of adenocarcinoma in prostate needle biopsy tissue. J. Clin. Pathol. 2007;60:35-42.
  35. Savolainen K., Bhaumik P., Schmitz W., Kotti T.J., Conzelmann E., Wierenga R.K., Hiltunen, J.K. Alpha-methylacyl-CoA racemase from Mycobacterium tuberculosis. Mutational and structural characterization of the active site and the fold. J. Biol. Chem. 2005;280:12611-12620.
  36. Bhaumik P., Schmitz W., Hassinen A., Hiltunen J. K., Conzelmann E., Wierenga R.K., Lloyd M.D. The catalysis of the 1,1-proton transfer by alpha-methyl-acyl-CoA racemase is coupled to a movement of the fatty acyl moiety over a hydrophobic, methionine-rich surface. J. Mol. Biol. 2007;367:1145-1161.
  37. Lloyd M.D., Darley D.J., Wierzbicki A.S., Threadgill M.D. Alpha-methylacyl-CoA racemase - an ‘obscure’ metabolic enzyme takes centre stage, FEBS J. 2008;275:1089-1102.
  38. Lloyd M.D., Yevglevskis M., Lee G.L., Wood P.J., Threadgill M.D., Woodman T. J. a-Methylacyl-CoA racemase (AMACR): metabolic enzyme, drug metabolizer and cancer marker P504S. Prog. Lipid Res. 2013;52:220-230.
  39. Jiang Z., Fanger G.R., Woda B.A., Banner B.F., Algate P., Dresser K., Xu J., Chu P.G. Expression of alpha-methylacyl-CoA racemase (P504s) in various malignant neoplasms and normal tissues: a study of 761 cases. Hum. Pathol. 2003;34:792-796.
  40. Baron A., Migita T., Tang D., Loda M. Fatty acid synthase: a metabolic oncogene in prostate cancer? J. Cell. Biochem. 2004;91:47-53.

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