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Article Open Access

Functional characteristics of cancer stem cells and their role in drug resistance of prostate cancer

  • Authors:
    • Viviana Castillo
    • Rodrigo Valenzuela
    • Christian Huidobro
    • Hector R. Contreras
    • Enrique A. Castellon
  • View Affiliations / Copyright

    Affiliations: Laboratory of Molecular and Cellular Andrology, Physiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380453, Chile, Urology Service, Clinical Hospital, University of Chile, Santiago 8380453, Chile
    Copyright: © Castillo et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 985-994
    |
    Published online on: June 27, 2014
       https://doi.org/10.3892/ijo.2014.2529
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Abstract

Cancer stem cells (CSCs) have the ability to self-renew and differentiate to give rise to heterogeneous phenotype of the tumor cells. It is believed that these cells are involved in metastasis, recurrence and therapy resistance in various cancers. CSCs have been identified in prostate cancer (PCa), one of the most diagnosed malignancies in men over the world, for which chemotherapy resistance is a major problem in the treatment of castration-resistant advanced stages. Molecular signatures, gene expression and functional features have been reported for PCa CSCs. Most data come from cell lines which may not represent the actual tumor. In the present work, a CSCs enriched population obtained from PCa explants was functionally characterized and analyzed for drug resistance. Tumorsphere cultures positive for ABCG2 transporter, CD133, CD44, cytokeratins 5 and 18 (CK5 and CK18) and negatives for androgen receptor (AR) and prostate-specific antigen (PSA) showed higher clonogenic capacity, holoclone-forming ability, colony-forming capacity in soft agar and lower proliferative and apoptotic rate than control adherent cell cultures. Furthermore, exposing tumorsphere cultures to ABCG2 substrate drugs resulted in a high survival rate compared with control PCa cells. This high drug resistance was decreased using a selective inhibitor of ABCG2. According to these results, tumorspheres from PCa explants showed a functional stem phenotype and a marked drug resistance, probably mediated by high expression of the ABCG2 transporter, which might be considered as a suitable therapeutic target for CSCs.
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View References

1 

Nagler C, Zanker KS and Dittmar T: Cell fusion, drug resistance and recurrence CSCs. Adv Exp Med Biol. 714:173–182. 2011. View Article : Google Scholar : PubMed/NCBI

2 

Barnhart BC and Simon MC: Metastasis and stem cell pathways. Cancer Metastasis Rev. 26:261–271. 2007. View Article : Google Scholar

3 

Kuhn NZ and Tuan RS: Regulation of stemness and stem cell niche of mesenchymal stem cells: implications in tumorigenesis and metastasis. J Cell Physiol. 222:268–277. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Hayashida T, Jinno H, Kitagawa Y, et al: Cooperation of cancer stem cell properties and epithelial-mesenchymal transition in the establishment of breast cancer metastasis. J Oncol. 2011:5914272011. View Article : Google Scholar : PubMed/NCBI

5 

Sampieri K and Fodde R: Cancer stem cells and metastasis. Semin Cancer Biol. 22:187–193. 2012. View Article : Google Scholar

6 

Chen SF, Chang YC, Nieh S, et al: Nonadhesive culture system as a model of rapid sphere formation with cancer stem cell properties. PLoS One. 7:e318642012. View Article : Google Scholar : PubMed/NCBI

7 

Tu SM and Lin SH: Prostate cancer stem cells. Clin Genitourin Cancer. 10:69–76. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Li H and Tang DG: Prostate cancer stem cells and their potential roles in metastasis. J Surg Oncol. 103:558–562. 2011. View Article : Google Scholar

9 

Siegel R, Ma J, Zou Z, et al: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar

10 

Tirino V, Desiderio V, Paino F, et al: Cancer stem cells in solid tumors: an overview and new approaches for their isolation and characterization. FASEB J. 27:13–24. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Sugihara E and Saya H: Complexity of cancer stem cells. Int J Cancer. 132:1249–1259. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Zhang Z, Filho MS and Nor JE: The biology of head and neck cancer stem cells. Oral Oncol. 48:1–9. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Castellon EA, Valenzuela R, Lillo J, et al: Molecular signature of cancer stem cells isolated from prostate carcinoma and expression of stem markers in different Gleason grades and metastasis. Biol Res. 45:297–305. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Fukaya R, Ohta S, Yamaguchi M, et al: Isolation of cancer stem-like cells from a side population of a human glioblastoma cell line, SK-MG-1. Cancer Lett. 291:150–157. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Hiraga T, Ito S and Nakamura H: Side population in MDA-MB-231 human breast cancer cells exhibits cancer stem cell-like properties without higher bone-metastatic potential. Oncol Rep. 25:289–296. 2011.

16 

Bleau AM, Huse JT and Holland EC: The ABCG2 resistance network of glioblastoma. Cell Cycle. 8:2936–2944. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Corcoran C, Rani S, O’Brien K, et al: Docetaxel-resistance in prostate cancer: evaluating associated phenotypic changes and potential for resistance transfer via exosomes. PLoS One. 7:e509992012. View Article : Google Scholar

18 

Singh S, Chitkara D, Mehrazin R, et al: Chemoresistance in prostate cancer cells is regulated by miRNAs and Hedgehog pathway. PLoS One. 7:e400212012. View Article : Google Scholar : PubMed/NCBI

19 

Semenas J, Allegrucci C, Boorjian SA, et al: Overcoming drug resistance and treating advanced prostate cancer. Curr Drug Targets. 13:1308–1323. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Cooperberg MR, Small EJ, D’Amico A, et al: The evolving role of androgen deprivation therapy in the management of prostate cancer. Minerva Urol Nefrol. 55:219–238. 2003.PubMed/NCBI

21 

Buyyounouski MK: Androgen deprivation therapy in high-risk prostate cancer. Oncology (Williston Park). 24:806–809. 2010.PubMed/NCBI

22 

Petrylak DP: Current state of castration-resistant prostate cancer. Am J Manag Care. 19(Suppl 18): S358–S365. 2013.PubMed/NCBI

23 

Sanchez C, Mercado A, Contreras HR, et al: Chemotherapy sensitivity recovery of prostate cancer cells by functional inhibition and knock down of multidrug resistance proteins. Prostate. 71:1810–1817. 2011. View Article : Google Scholar

24 

Sanchez C, Mendoza P, Contreras HR, et al: Expression of multidrug resistance proteins in prostate cancer is related with cell sensitivity to chemotherapeutic drugs. Prostate. 69:1448–1459. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Kerfoot C, Huang W and Rotenberg SA: Immunohistochemical analysis of advanced human breast carcinomas reveals downregulation of protein kinase C alpha. J Histochem Cytochem. 52:419–422. 2004. View Article : Google Scholar : PubMed/NCBI

26 

Franken NA, Rodermond HM, Stap J, et al: Clonogenic assay of cells in vitro. Nat Protoc. 1:2315–2319. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Li H, Chen X, Calhoun-Davis T, et al: PC3 human prostate carcinoma cell holoclones contain self-renewing tumor-initiating cells. Cancer Res. 68:1820–1825. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Zhang L, Jiao M, Li L, et al: Tumorspheres derived from prostate cancer cells possess chemoresistant and cancer stem cell properties. J Cancer Res Clin Oncol. 138:675–686. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Bisson I and Prowse DM: WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics. Cell Res. 19:683–697. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Freitas DP, Teixeira CA, Santos-Silva F, et al: Therapy-induced enrichment of putative lung cancer stem-like cells. Int J Cancer. 134:1270–1278. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Ratajczak M, Tarnowski M, Staniszewska M, et al: Mechanisms of cancer metastasis: involvement of cancer stem cells? Minerva Med. 101:179–191. 2010.PubMed/NCBI

32 

Chen X, Rycaj K, Liu X, et al: New insights into prostate cancer stem cells. Cell Cycle. 12:579–586. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Miki J: Investigations of prostate epithelial stem cells and prostate cancer stem cells. Int J Urol. 17:139–147. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Wang L, Huang X, Zheng X, et al: Enrichment of prostate cancer stem-like cells from human prostate cancer cell lines by culture in serum-free medium and chemoradiotherapy. Int J Biol Sci. 9:472–479. 2013. View Article : Google Scholar : PubMed/NCBI

35 

Garraway IP, Sun W, Tran CP, et al: Human prostate sphere-forming cells represent a subset of basal epithelial cells capable of glandular regeneration in vivo. Prostate. 70:491–501. 2010.

36 

Sutton LM, Han JS, Molberg KH, et al: Intratumoral expression level of epidermal growth factor receptor and cytokeratin 5/6 is significantly associated with nodal and distant metastases in patients with basal-like triple-negative breast carcinoma. Am J Clin Pathol. 134:782–787. 2010. View Article : Google Scholar

37 

de Silva Rudland S, Platt-Higgins A, Winstanley JH, et al: Statistical association of basal cell keratins with metastasis-inducing proteins in a prognostically unfavorable group of sporadic breast cancers. Am J Pathol. 179:1061–1072. 2011.PubMed/NCBI

38 

Celia-Terrassa T, Meca-Cortes O, Mateo F, et al: Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells. J Clin Invest. 122:1849–1868. 2012. View Article : Google Scholar

39 

Patrawala L, Calhoun-Davis T, Schneider-Broussard R, et al: Hierarchical organization of prostate cancer cells in xenograft tumors: the CD44+alpha2beta1+cell population is enriched in tumor-initiating cells. Cancer Res. 67:6796–6805. 2007. View Article : Google Scholar : PubMed/NCBI

40 

Patrawala L, Calhoun T, Schneider-Broussard R, et al: Highly purified CD44+prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene. 25:1696–1708. 2006.

41 

Kee N, Sivalingam S, Boonstra R, et al: The utility of Ki-67 and BrdU as proliferative markers of adult neurogenesis. J Neurosci Methods. 115:97–105. 2002. View Article : Google Scholar : PubMed/NCBI

42 

Coltrera MD and Gown AM: PCNA/cyclin expression and BrdU uptake define different subpopulations in different cell lines. J Histochem Cytochem. 39:23–30. 1991. View Article : Google Scholar : PubMed/NCBI

43 

Staszkiewicz J, Gimble J, Cain C, et al: Flow cytometric and immunohistochemical detection of in vivo BrdU-labeled cells in mouse fat depots. Biochem Biophys Res Commun. 378:539–544. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Castillo V, Valenzuela R, Huidobro C, Contreras HR and Castellon EA: Functional characteristics of cancer stem cells and their role in drug resistance of prostate cancer. Int J Oncol 45: 985-994, 2014.
APA
Castillo, V., Valenzuela, R., Huidobro, C., Contreras, H.R., & Castellon, E.A. (2014). Functional characteristics of cancer stem cells and their role in drug resistance of prostate cancer. International Journal of Oncology, 45, 985-994. https://doi.org/10.3892/ijo.2014.2529
MLA
Castillo, V., Valenzuela, R., Huidobro, C., Contreras, H. R., Castellon, E. A."Functional characteristics of cancer stem cells and their role in drug resistance of prostate cancer". International Journal of Oncology 45.3 (2014): 985-994.
Chicago
Castillo, V., Valenzuela, R., Huidobro, C., Contreras, H. R., Castellon, E. A."Functional characteristics of cancer stem cells and their role in drug resistance of prostate cancer". International Journal of Oncology 45, no. 3 (2014): 985-994. https://doi.org/10.3892/ijo.2014.2529
Copy and paste a formatted citation
x
Spandidos Publications style
Castillo V, Valenzuela R, Huidobro C, Contreras HR and Castellon EA: Functional characteristics of cancer stem cells and their role in drug resistance of prostate cancer. Int J Oncol 45: 985-994, 2014.
APA
Castillo, V., Valenzuela, R., Huidobro, C., Contreras, H.R., & Castellon, E.A. (2014). Functional characteristics of cancer stem cells and their role in drug resistance of prostate cancer. International Journal of Oncology, 45, 985-994. https://doi.org/10.3892/ijo.2014.2529
MLA
Castillo, V., Valenzuela, R., Huidobro, C., Contreras, H. R., Castellon, E. A."Functional characteristics of cancer stem cells and their role in drug resistance of prostate cancer". International Journal of Oncology 45.3 (2014): 985-994.
Chicago
Castillo, V., Valenzuela, R., Huidobro, C., Contreras, H. R., Castellon, E. A."Functional characteristics of cancer stem cells and their role in drug resistance of prostate cancer". International Journal of Oncology 45, no. 3 (2014): 985-994. https://doi.org/10.3892/ijo.2014.2529
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