Skip to main content
SpringerLink
Log in

Prostate Tumor Cell Plasticity: A Consequence of the Microenvironment

  • Chapter
  • First Online:
Human Cell Transformation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 720))

Abstract

During each step of prostate cancer metastasis, cancer displays phenotypic plasticity that is associated with the expression of both epithelial and mesenchymal properties or an epithelial to mesenchymal transition. This phenotypic transition is typically in response to microenvironment signals and is the basis for basic cancer cell survival (e.g. motility and invasion versus proliferation). In this review we discuss the loss and gain of E-cadherin expression as a marker of tumor plasticity throughout the steps of metastasis, and particularly focus on dynamic tumor–stromal interaction that induce a cancer cell-associated mesenchymal to epithelial reverting transition in the bone and liver microenvironments.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kahn LB, Uys CJ, Dale J, Rutherfoord S (1978) Carcinoma of the breast with metaplasia to chondrosarcoma: a light and electron microscopic study. Histopathology 2:93–106

    Article  PubMed  CAS  Google Scholar 

  2. Hay ED, Zuk A (1995) Transformations between ­epithelium and mesenchyme: normal, pathological, and experimentally induced. Am J Kidney Dis 26:678–690

    Article  PubMed  CAS  Google Scholar 

  3. Ehrlich JS, Hansen MD, Nelson WJ (2002) Spatio-temporal regulation of Rac1 localization and lamellipodia dynamics during epithelial cell-cell adhesion. Dev Cell 3:259–270

    Article  PubMed  CAS  Google Scholar 

  4. Akhtar N, Hudson KR, Hotchin NA (2000) Co-localization of Rac1 and E-cadherin in human epidermal keratinocytes. Cell Adhes Commun 7:465–476

    Article  PubMed  CAS  Google Scholar 

  5. Ray ME, Mehra R, Sandler HM, Daignault S, Shah RB (2006) E-cadherin protein expression predicts prostate cancer salvage radiotherapy outcomes. J Urol 176:1409–1414, discussion 14

    Article  PubMed  CAS  Google Scholar 

  6. Hennig G, Behrens J, Truss M, Frisch S, Reichmann E, Birchmeier W (1995) Progression of carcinoma cells is associated with alterations in chromatin structure and factor binding at the E-cadherin promoter in vivo. Oncogene 11:475–484

    PubMed  CAS  Google Scholar 

  7. Graff JR, Herman JG, Lapidus RG et al (1995) E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. Cancer Res 55:5195–5199

    PubMed  CAS  Google Scholar 

  8. Machado JC, Oliveira C, Carvalho R et al (2001) E-cadherin gene (CDH1) promoter methylation as the second hit in sporadic diffuse gastric carcinoma. Oncogene 20:1525–1528

    Article  PubMed  CAS  Google Scholar 

  9. Berx G, Becker KF, Hofler H, van Roy F (1998) Mutations of the human E-cadherin (CDH1) gene. Hum Mutat 12:226–237

    Article  PubMed  CAS  Google Scholar 

  10. Hirohashi S (1998) Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol 153:333–339

    Article  PubMed  CAS  Google Scholar 

  11. Jennbacken K, Tesan T, Wang W, Gustavsson H, Damber JE, Welen K (2010) N-cadherin increases after androgen deprivation and is associated with metastasis in prostate cancer. Endocr Relat Cancer 17:469–479

    Article  PubMed  CAS  Google Scholar 

  12. Tanaka H, Kono E, Tran CP et al (2010) Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance. Nat Med 16:1414–1420

    Article  PubMed  CAS  Google Scholar 

  13. Tran NL, Nagle RB, Cress AE, Heimark RL (1999) N-cadherin expression in human prostate carcinoma cell lines. An epithelial-mesenchymal transformation mediating adhesion with stromal cells. Am J Pathol 155:787–798

    Article  PubMed  CAS  Google Scholar 

  14. Odero-Marah VA, Wang R, Chu G et al (2008) Receptor activator of NF-kappaB ligand (RANKL) expression is associated with epithelial to mesenchymal transition in human prostate cancer cells. Cell Res 18:858–870

    Article  PubMed  CAS  Google Scholar 

  15. Liu J, Uygur B, Zhang Z et al (2010) Slug inhibits proliferation of human prostate cancer cells via downregulation of cyclin D1 expression. Prostate 70:1768–1777

    PubMed  CAS  Google Scholar 

  16. Emadi Baygi M, Soheili ZS, Schmitz I, Sameie S, Schulz WA (2010) Snail regulates cell survival and inhibits cellular senescence in human metastatic prostate cancer cell lines. Cell Biol Toxicol 26:553–567

    Article  PubMed  CAS  Google Scholar 

  17. Kwok WK, Ling MT, Lee TW et al (2005) Up-regulation of TWIST in prostate cancer and its implication as a therapeutic target. Cancer Res 65:5153–5162

    Article  PubMed  CAS  Google Scholar 

  18. Yuen HF, Chan YP, Wong ML et al (2007) Upregulation of twist in oesophageal squamous cell carcinoma is associated with neoplastic transformation and distant metastasis. J Clin Pathol 60:510–514

    Article  PubMed  CAS  Google Scholar 

  19. Downing JR, Reynolds AB (1991) PDGF, CSF-1, and EGF induce tyrosine phosphorylation of p120, a pp 60src transformation-associated substrate. Oncogene 6:607–613

    PubMed  CAS  Google Scholar 

  20. Hazan RB, Norton L (1998) The epidermal growth factor receptor modulates the interaction of E-cadherin with the actin cytoskeleton. J Biol Chem 273:9078–9084

    Article  PubMed  CAS  Google Scholar 

  21. Andl CD, Mizushima T, Nakagawa H et al (2003) Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo. J Biol Chem 278:1824–1830

    Article  PubMed  CAS  Google Scholar 

  22. Kassis J, Moellinger J, Lo H, Greenberg NM, Kim HG, Wells A (1999) A role for phospholipase C-gamma-mediated signaling in tumor cell invasion. Clin Cancer Res 5:2251–2260

    PubMed  CAS  Google Scholar 

  23. Nakashiro K, Okamoto M, Hayashi Y, Oyasu R (2000) Hepatocyte growth factor secreted by prostate-derived stromal cells stimulates growth of androgen-­independent human prostatic carcinoma cells. Am J Pathol 157:795–803

    Article  PubMed  CAS  Google Scholar 

  24. Yates C, Wells A, Turner T (2005) Luteinising ­hormone-releasing hormone analogue reverses the cell adhesion profile of EGFR overexpressing DU-145 human prostate carcinoma subline. Br J Cancer 92:366–375

    PubMed  CAS  Google Scholar 

  25. Davies G, Jiang WG, Mason MD (2001) HGF/SF modifies the interaction between its receptor c-Met, and the E-cadherin/catenin complex in prostate cancer cells. Int J Mol Med 7:385–388

    PubMed  CAS  Google Scholar 

  26. Josson S, Anderson CS, Sung SY et al (2011) Inhibition of ADAM9 expression induces epithelial phenotypic alterations and sensitizes human prostate cancer cells to radiation and chemotherapy. Prostate 71(3):232–240

    Article  PubMed  CAS  Google Scholar 

  27. Graham TR, Zhau HE, Odero-Marah VA et al (2008) Insulin-like growth factor-I-dependent up-regulation of ZEB1 drives epithelial-to-mesenchymal transition in human prostate cancer cells. Cancer Res 68:2479–2488

    Article  PubMed  CAS  Google Scholar 

  28. Yates C, Shepard CR, Papworth G et al (2007) Novel three-dimensional organotypic liver bioreactor to directly visualize early events in metastatic progression. Adv Cancer Res 97:225–246

    Article  PubMed  Google Scholar 

  29. Yates CC, Shepard CR, Stolz DB, Wells A (2007) Co-culturing human prostate carcinoma cells with hepatocytes leads to increased expression of E-cadherin. Br J Cancer 96:1246–1252

    Article  PubMed  CAS  Google Scholar 

  30. Li LC, Zhao H, Nakajima K et al (2001) Methylation of the E-cadherin gene promoter correlates with progression of prostate cancer. J Urol 166:705–709

    Article  PubMed  CAS  Google Scholar 

  31. Ma L, Teruya-Feldstein J, Weinberg RA (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449:682–688

    Article  PubMed  CAS  Google Scholar 

  32. Lehmann U, Hasemeier B, Christgen M et al (2008) Epigenetic inactivation of microRNA gene hsa-mir-9-1 in human breast cancer. J Pathol 214:17–24

    Article  PubMed  CAS  Google Scholar 

  33. Dalmay T, Edwards DR (2006) MicroRNAs and the hallmarks of cancer. Oncogene 25:6170–6175

    Article  PubMed  CAS  Google Scholar 

  34. Kong D, Li Y, Wang Z et al (2009) miR-200 regulates PDGF-D-mediated epithelial-mesenchymal transition, adhesion, and invasion of prostate cancer cells. Stem Cells 27:1712–1721

    Article  PubMed  CAS  Google Scholar 

  35. Wu TT, Sikes RA, Cui Q et al (1998) Establishing human prostate cancer cell xenografts in bone: induction of osteoblastic reaction by prostate-specific antigen-producing tumors in athymic and SCID/bg mice using LNCaP and lineage-derived metastatic sublines. Int J Cancer 77:887–894

    Article  PubMed  CAS  Google Scholar 

  36. Zhau HE, Li CL, Chung LW (2000) Establishment of human prostate carcinoma skeletal metastasis models. Cancer 88:2995–3001

    Article  PubMed  CAS  Google Scholar 

  37. Paget S (1889) The distribution of secondary growths in cancer of the breast. Cancer Metastasis Rev 8:98–101

    Google Scholar 

  38. Chung LW (2003) Prostate carcinoma bone-stroma interaction and its biologic and therapeutic implications. Cancer 97:772–778

    Article  PubMed  Google Scholar 

  39. Stessels F, Van den Eynden G, Van der Auwera I et al (2004) Breast adenocarcinoma liver metastases, in contrast to colorectal cancer liver metastases, display a non-angiogenic growth pattern that preserves the stroma and lacks hypoxia. Br J Cancer 90:1429–1436

    Article  PubMed  CAS  Google Scholar 

  40. Buijs JT, Rentsch CA, van der Horst G et al (2007) BMP7, a putative regulator of epithelial homeostasis in the human prostate, is a potent inhibitor of prostate cancer bone metastasis in vivo. Am J Pathol 171:1047–1057

    Article  PubMed  CAS  Google Scholar 

  41. Morrissey C, True LD, Roudier MP et al (2008) Differential expression of angiogenesis associated genes in prostate cancer bone, liver and lymph node metastases. Clin Exp Metastasis 25:377–388

    Article  PubMed  CAS  Google Scholar 

  42. Josson S, Sharp S, Sung SY (2010) et al. Tumor-stromal interactions influence radiation sensitivity in epithelial – versus mesenchymal-like prostate cancer cells, J Oncol

    Google Scholar 

  43. Saha B, Kaur P, Tsao-Wei D et al (2008) Unmethylated E-cadherin gene expression is significantly associated with metastatic human prostate cancer cells in bone. Prostate 68:1681–1688

    Article  PubMed  CAS  Google Scholar 

  44. Green SK, Karlsson MC, Ravetch JV, Kerbel RS (2002) Disruption of cell-cell adhesion enhances antibody-dependent cellular cytotoxicity: implications for antibody-based therapeutics of cancer. Cancer Res 62:6891–6900

    PubMed  CAS  Google Scholar 

  45. Lamb LE, Knudsen BS, Miranti CK (2010) E-cadherin-mediated survival of androgen-receptor-expressing secretory prostate epithelial cells derived from a stratified in vitro differentiation model. J Cell Sci 123:266–276

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

I would like to acknowledge all ­collaborators involved in the different phases of this work. This work was funded by grant from the Department of Defense Prostate Cancer Research Program (PC073977), and NIH/RCMI G12 RR03059-21A1.

Author information

Authors and Affiliations

  1. Department of Biology and Center for Cancer Research, Tuskegee University, Tuskegee, AL, 36088, USA

    Clayton Yates

Authors
  1. Clayton Yates
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Clayton Yates .

Editor information

Editors and Affiliations

  1. Uniformed Services, Department of Surgery, University of the Health Sciences, South Glen Road 11455, Bethesda, 20854, Maryland, USA

    Johng S. Rhim

  2. , Department of Medicine, McGill University Health Centre, Pine Ave 687, Montreal, Québec, Canada

    Richard Kremer

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Yates, C. (2011). Prostate Tumor Cell Plasticity: A Consequence of the Microenvironment. In: Rhim, J., Kremer, R. (eds) Human Cell Transformation. Advances in Experimental Medicine and Biology, vol 720. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0254-1_7

Download citation

Publish with us

Policies and ethics

Search

Navigation