The evolving landscape of prostate cancer stem cell: Therapeutic implications and future challenges

Asian Journal of Urology, 2016, 3 (4): 203-210 doi:

Review

Current Issue | Archive | Adv Search

The evolving landscape of prostate cancer stem cell: Therapeutic implications and future challenges

Eun-Jin Yun, U-Ging Lo, Jer-Tsong Hsieh

Department of Urology, UT Southwestern Medical Center, Dallas, TX, USA

Abstract
Related Citation (15)

Download:

HTML

PDF (2378KB)
Export: BibTeX | EndNote (RIS)

Abstract Prostate cancer (PCa) is the most common cause of malignancy in males and the second leading cause of cancer mortality in United States. Current treatments for PCa include surgery, radiotherapy, and androgen-deprivation therapy. Eventually, PCa relapses to an advanced castration-resistant PCa (CRPC) that becomes a systematic disease and incurable. Therefore, identifying cellular components and molecular mechanisms that drive aggressive PCa at early stage is critical for disease prognosis and therapeutic intervention. One potential strategy for aggressive PCa is to target cancer stem cells (CSCs) that are identified by several unique characteristics such as immortal, self-renewal, and pluripotency. Also, CSC is believed to be a major factor contributing to resistance to radiotherapy and conventional chemotherapies. Moreover, CSCs are thought to be the critical cause of metastasis, tumor recurrence and cancer-related death of multiple cancer types, including PCa. In this review, we discuss recent progress made in understanding prostate cancer stem cells (PCSCs). We focus on the therapeutic strategies aimed at targeting specific surface markers of CSCs, the key signaling pathways in the maintenance of self-renewal capacity of CSCs, ATP-binding cassette (ABC) transporters that mediate the drug-resistance of CSCs, dysregulated microRNAs expression profiles in CSCs, and immunotherapeutic strategies developed against PCSCs surface markers.

Key words： Prostate cancer Cancer stem cell Normal stem cell

Received: 07 June 2016 Published: 02 November 2016

	Service
	E-mail this article
	Add to citation manager
	E-mail Alert
	Articles by authors
	Eun-Jin Yun
	U-Ging Lo
	Jer-Tsong Hsieh

TRENDMD:

Cite this article:

Eun-Jin Yun,U-Ging Lo,Jer-Tsong Hsieh. The evolving landscape of prostate cancer stem cell: Therapeutic implications and future challenges[J]. Asian Journal of Urology, 2016, 3(4): 203-210.

URL:

http://www.ajurology.com/EN/ OR http://www.ajurology.com/EN/Y2016/V3/I4/203

[1]	Torre LA, Siegel RL, Ward EM, Jemal A. Global cancer incidence and mortality rates and trendsean update. Cancer Epidemiol Biomarkers Prev 2016;25:16-27.
[2]	Partin AW, Kattan MW, Subong EN, Walsh PC, Wojno KJ, Oesterling JE, et al. Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update. JAMA 1997;277:1445-51.
[3]	Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997;3:730-7.
[4]	Maitland NJ, Collins AT. Inflammation as the primary aetiological agent of human prostate cancer:a stem cell connection? J Cell Biochem 2008;105:931-9.
[5]	Al-Hajj M, Becker MW, Wicha M, Weissman I, Clarke MF. Therapeutic implications of cancer stem cells. Curr Opin Genet Dev 2004;14:43-7.
[6]	Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006;444:756-60.
[7]	Spangrude GJ, Heimfeld S, Weissman IL. Purification and characterization of mouse hematopoietic stem cells. Science 1988;241:58-62.
[8]	Morrison SJ, Shah NM, Anderson DJ. Regulatory mechanisms in stem cell biology. Cell 1997;88:287-98.
[9]	Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, et al. Cancer stem cellseperspectives on current status and future directions:AACR Workshop on cancer stem cells. Cancer Res 2006;66:9339-44.
[10]	Abate-Shen C, Shen MM. Molecular genetics of prostate cancer. Genes Dev 2000;14:2410-34.
[11]	Bonkhoff H, Remberger K. Widespread distribution of nuclear androgen receptors in the basal cell layer of the normal and hyperplastic human prostate. Virchows Arch 1993;422:35-8.
[12]	Liu AY, True LD, LaTray L, Nelson PS, Ellis WJ, Vessella RL, et al. Cell-cell interaction in prostate gene regulation and cytodifferentiation. Proc Natl Acad Sci USA 1997;94:10705-10.
[13]	Signoretti S, Waltregny D, Dilks J, Isaac B, Lin D, Garraway L, et al. p63 is a prostate basal cell marker and is required for prostate development. Am J Pathol 2000;157:1769-75.
[14]	Tang DG, Patrawala L, Calhoun T, Bhatia B, Choy G, SchneiderBroussard R, et al. Prostate cancer stem/progenitor cells:identification, characterization, and implications. Mol Carcinog 2007;46:1-14.
[15]	Kyprianou N, Isaacs JT. Identification of a cellular receptor for transforming growth factor-beta in rat ventral prostate and its negative regulation by androgens. Endocrinology 1988;123:2124-31.
[16]	De Marzo AM, Meeker AK, Epstein JI, Coffey DS. Prostate stem cell compartments:expression of the cell cycle inhibitor p27Kip1 in normal, hyperplastic, and neoplastic cells. Am J Pathol 1998;153:911-9.
[17]	Wang ZA, Mitrofanova A, Bergren SK, Abate-Shen C, Cardiff RD, Califano A, et al. Lineage analysis of basal epithelial cells reveals their unexpected plasticity and supports a cell-of-origin model for prostate cancer heterogeneity. Nat Cell Biol 2013;15:274-83.
[18]	Xin L, Lawson DA, Witte ON. The Sca-1 cell surface marker enriches for a prostate-regenerating cell subpopulation that can initiate prostate tumorigenesis. Proc Natl Acad Sci USA 2005;102:6942-7.
[19]	Lawson DA, Xin L, Lukacs RU, Cheng D, Witte ON. Isolation and functional characterization of murine prostate stem cells. Proc Natl Acad Sci USA 2007;104:181-6.
[20]	Goldstein AS, Huang J, Guo C, Garraway IP, Witte ON. Identification of a cell of origin for human prostate cancer. Science 2010;329:568-71.
[21]	Germann M, Wetterwald A, Guzman-Ramirez N, van der Pluijm G, Culig Z, Cecchini MG, et al. Stem-like cells with luminal progenitor phenotype survive castration in human prostate cancer. Stem Cells 2012;30:1076-86.
[22]	Smith BA, Sokolov A, Uzunangelov V, Baertsch R, Newton Y, Graim K, et al. A basal stem cell signature identifies aggressive prostate cancer phenotypes. Proc Natl Acad Sci USA 2015;112:E6544-52.
[23]	Wang X, Kruithof-de Julio M, Economides KD, Walker D, Yu H, Halili MV, et al. A luminal epithelial stem cell that is a cell of origin for prostate cancer. Nature 2009;461:495-500.
[24]	Karthaus WR, Iaquinta PJ, Drost J, Gracanin A, van Boxtel R, Wongvipat J, et al. Identification of multipotent luminal progenitor cells in human prostate organoid cultures. Cell 2014; 159:163-75.
[25]	Wang JC. Good cells gone bad:the cellular origins of cancer. Trends Mol Med 2010;16:145-51.
[26]	Rizvi AZ, Swain JR, Davies PS, Bailey AS, Decker AD, Willenbring H, et al. Bone marrow-derived cells fuse with normal and transformed intestinal stem cells. Proc Natl Acad Sci USA 2006;103:6321-5.
[27]	Kasper S. Exploring the origins of the normal prostate and prostate cancer stem cell. Stem Cell Rev 2008;4:193-201.
[28]	Taylor RA, Risbridger GP. The path toward identifying prostatic stem cells. Differentiation 2008;76:671-81.
[29]	Richardson GD, Robson CN, Lang SH, Neal DE, Maitland NJ, Collins AT. CD133, a novel marker for human prostatic epithelial stem cells. J Cell Sci 2004;117:3539-45.
[30]	Oxley SM, Sackstein R. Detection of an L-selectin ligand on a hematopoietic progenitor cell line. Blood 1994;84:3299-306.
[31]	Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, et al. Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 2006;25:1696-708.
[32]	Hurt EM, Kawasaki BT, Klarmann GJ, Thomas SB, Farrar WL. CD44+CD24 prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis. BJC 2008;98:756-65.
[33]	Holmes C, Stanford WL. Concise review:stem cell antigen-1:expression, function, and enigma. Stem Cells 2007;25:1339-47.
[34]	Mundy GR. Metastasis to bone:causes, consequences and therapeutic opportunities. Nat Rev Cancer 2002;2:584-93.
[35]	Patrawala L, Calhoun T, Schneider-Broussard R, Zhou J, Claypool K, Tang DG. Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2 cancer cells are similarly tumorigenic. Cancer Res 2005;65:6207-19.
[36]	Li Y, Cozzi PJ, Russell PJ. Promising tumor-associated antigens for future prostate cancer therapy. Med Res Rev 2010;30:67-101.
[37]	Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 2005;65:10946-51.
[38]	Patrawala L, Calhoun-Davis T, Schneider-Broussard R, Tang DG. Hierarchical organization of prostate cancer cells in xenograft tumors:the CD44+α2β1+ cell population is enriched in tumorinitiating cells. Cancer Res 2007;67:6796-805.
[39]	Sharifi N, Kawasaki BT, Hurt EM, Farrar WL. Stem cells in prostate cancer:resolving the castrate-resistant conundrum and implications for hormonal therapy. Cancer Biol Ther 2006; 5:901-6.
[40]	Kong D, Heath E, Chen W, Cher ML, Powell I, Heilbrun L, et al. Loss of let-7 up-regulates EZH2 in prostate cancer consistent with the acquisition of cancer stem cell signatures that are attenuated by BR-DIM. PLoS One 2012;7:e33729.
[41]	Carson 3rd CC. Carcinoma of the prostate:overview of the most common malignancy in men. N C Med J 2006;67:122-7.
[42]	Harrison DE, Lerner CP. Most primitive hematopoietic stem cells are stimulated to cycle rapidly after treatment with 5-fluorouracil. Blood 1991;78:1237-40.
[43]	Deeley RG, Westlake C, Cole SP. Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Physiol Rev 2006;86:849-99.
[44]	Zhang L, Jiao M, Li L, Wu D, Wu K, Li X, et al. Tumorspheres derived from prostate cancer cells possess chemoresistant and cancer stem cell properties. J Cancer Res Clin Oncol 2012;138:675-86.
[45]	Bhattacharya S, Das A, Mallya K, Ahmad I. Maintenance of retinal stem cells by Abcg2 is regulated by notch signaling. J Cell Sci 2007;120:2652-62.
[46]	Bleau AM, Hambardzumyan D, Ozawa T, Fomchenko EI, Huse JT, Brennan CW, et al. PTEN/PI3K/Akt pathway regulates the side population phenotype and ABCG2 activity in glioma tumor stem-like cells. Cell stem cell 2009;4:226-35.
[47]	Sims-Mourtada J, Izzo JG, Ajani J, Chao KS. Sonic Hedgehog promotes multiple drug resistance by regulation of drug transport. Oncogene 2007;26:5674-9.
[48]	Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer 2005;5:275-84.
[49]	Tagscherer KE, Fassl A, Campos B, Farhadi M, Kraemer A, Bock BC, et al. Apoptosis-based treatment of glioblastomas with ABT-737, a novel small molecule inhibitor of Bcl-2 family proteins. Oncogene 2008;27:6646-56.
[50]	Sung SY, Liao CH, Wu HP, Hsiao WC, Wu IH, Jinpu, et al. Loss of let-7 microRNA upregulates IL-6 in bone marrow-derived mesenchymal stem cells triggering a reactive stromal response to prostate cancer. PLoS One 2013;8:e71637.
[51]	Eriksson D, Stigbrand T. Radiation-induced cell death mechanisms. Tumour Biol 2010;31:363-72.
[52]	Colombel M, Eaton CL, Hamdy F, Ricci E, van der Pluijm G, Cecchini M, et al. Increased expression of putative cancer stem cell markers in primary prostate cancer is associated with progression of bone metastases. Prostate 2012;72:713-20.
[53]	Ricci E, Mattei E, Dumontet C, Eaton CL, Hamdy F, van der Pluije G, et al. Increased expression of putative cancer stem cell markers in the bone marrow of prostate cancer patients is associated with bone metastasis progression. Prostate 2013; 73:1738-46.
[54]	Guzel E, Karatas OF, Duz MB, Solak M, Ittmann M, Ozen M. Differential expression of stem cell markers and ABCG2 in recurrent prostate cancer. Prostate 2014;74:1498-505.
[55]	Guzmán-Ramírez N, Voller M, Wetterwald A, Germann M, Cross NA, Rentsch CA, et al. In vitro propagation and characterization of neoplastic stem/progenitor-like cells from human prostate cancer tissue. Prostate 2009;69:1683-93.
[56]	Takebe N, Miele L, Harris PJ, Jeong W, Bando H, Kahn M, et al. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells:clinical update. Nat Rev Clin Oncol 2015;12:445-64.
[57]	Kar S, Deb M, Sengupta D, Shilpi A, Bhutia SK, Patra SK. Intricacies of hedgehog signaling pathways:a perspective in tumorigenesis. Exp Cell Res 2012;318:1959-72.
[58]	Sanchez P, Hernandez AM, Stecca B, Kahler AJ, DeGueme AM, Barrett A, et al. Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Natl Acad Sci USA 2004;101:12561-6.
[59]	Zhang Y, Wang Z, Ahmed F, Banerjee S, Li Y, Sarkar FH. Downregulation of Jagged-1 induces cell growth inhibition and S phase arrest in prostate cancer cells. Int J Cancer 2006;119:2071-7.
[60]	Zhu H, Zhou X, Redfield S, Lewin J, Miele L. Elevated Jagged-1 and Notch-1 expression in high grade and metastatic prostate cancers. Am J Transl Res 2013;5:368-78.
[61]	Domingo-Domenech J, Vidal SJ, Rodriguez-Bravo V, CastilloMartin M, Quinn SA, Rodriguez-Barrueco R, et al. Suppression of acquired docetaxel resistance in prostate cancer through depletion of notch- and hedgehog-dependent tumor-initiating cells. Cancer cell 2012;22:373-88.
[62]	Fan X, Matsui W, Khaki L, Stearns D, Chun J, Li YM, et al. Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors. Cancer Res 2006;66:7445-52.
[63]	Bisson I, Prowse DM. WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics. Cell Res 2009;19:683-97.
[64]	Lee E, Madar A, David G, Garabedian MJ, Dasgupta R, Logan SK. Inhibition of androgen receptor and beta-catenin activity in prostate cancer. Proc Natl Acad Sci USA 2013;110:15710-5.
[65]	Liu C, Kelnar K, Vlassov AV, Brown D, Wang J, Tang DG. Distinct microRNA expression profiles in prostate cancer stem/progenitor cells and tumor-suppressive functions of let-7. Cancer Res 2012;72:3393-404.
[66]	Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, et al. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med 2011;17:211-5.
[67]	Fan X, Chen X, Deng W, Zhong G, Cai Q, Lin T. Up-regulated microRNA-143 in cancer stem cells differentiation promotes prostate Cancer cells metastasis by modulating FNDC3B expression. BMC Cancer 2013;13:61.
[68]	Hsieh IS, Chang KC, Tsai YT, Ke JY, Lu PJ, Lee KH, et al. MicroRNA-320 suppresses the stem cell-like characteristics of prostate cancer cells by downregulating the Wnt/betacatenin signaling pathway. Carcinogenesis 2013;34:530-8.
[69]	Huang S, Guo W, Tang Y, Ren D, Zou X, Peng X. miR-143 and miR-145 inhibit stem cell characteristics of PC-3 prostate cancer cells. Oncol Rep 2012;28:1831-7.
[70]	Yu J, Lu Y, Cui D, Li E, Zhu Y, Zhao Y, et al. miR-200b suppresses cell proliferation, migration and enhances chemosensitivity in prostate cancer by regulating Bmi-1. Oncol Rep 2014;31:910-8.
[71]	Dudley ME, Wunderlich JR, Yang JC, Sherry RM, Topalian SL, Restifo NP, et al. Adoptive cell transfer therapy following nonmyeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol 2005;23:2346-57.
[72]	June CH. Adoptive T cell therapy for cancer in the clinic. J Clin Invest. 2007;117:1466-76.
[73]	Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006;314:126-9.
[74]	Park JR, Digiusto DL, Slovak M, Wright C, Naranjo A, Wagner J, et al. Adoptive transfer of chimeric antigen receptor redirected cytolytic T lymphocyte clones in patients with neuroblastoma. Mol Ther 2007;15:825-33.
[75]	Deng Z, Wu Y, Ma W, Zhang S, Zhang YQ. Adoptive T-cell therapy of prostate cancer targeting the cancer stem cell antigen EpCAM. BMC Immunol 2015;16:1.
[76]	Cheng CY, Hwang CI, Corney DC, Flesken-Nikitin A, Jiang L, Oner GM, et al. miR-34 cooperates with p53 in suppression of prostate cancer by joint regulation of stem cell compartment. Cell Rep 2014;6:1000-7.
[77]	Wang M, Ren D, Guo W, Wang Z, Huang S, Du H, et al. Loss of miR-100 enhances migration, invasion, epithelial-mesenchymal transition and stemness properties in prostate cancer cells through targeting Argonaute 2. Int J Oncol 2014;45:362-72.