Tumorspheres derived from prostate cancer cells possess chemoresistant and cancer stem cell properties
- 1.5k Downloads
Prostate cancer (PCa) becomes lethal when cancer cells develop into castration-resistant PCa, which remains incurable because of the poor understanding of their cell origin and characteristics. We aim to investigate the potential role of cancer stem cells (CSCs) in PCa progression.
Human PCa cell lines (LNCaP, 22RV1, DU145 and PC-3) were plated in serum-free suspension culture system allowed for tumorsphere forming. To evaluate the CSC characteristics of tumorspheres, the self-renewal, chemoresistance, tumorigenicity of the PCa tumorsphere cells, and the expression levels of stemness-related proteins in the PCa tumorsphere cells were assessed, comparing with the parental adherent cells.
Tumorsphere cells from PCa cell lines displayed enhanced self-renewal, chemoresistance and tumor-initiating capacity when compared with the adherent cells. Additionally, these cells overexpressed CSC marker CD44. Also, the tumorsphere cells expressed high levels of “stemness” genes Gli1, ABCG2 and Bmi-1.
Collectively, these data demonstrated that tumorspheres derived from PCa cells possess chemoresistant and CSC properties. Our study suggests that the identification of PCa CSCs could provide new insight into the lethal phenotype of PCa and therapeutic implications.
KeywordsProstate cancer Cancer stem cell Chemoresistance Tumorsphere Stemness
This study was supported by a grant from National Natural Science Foundation of China (No. 30801152 to LL Zhang).
Conflict of interest
We declare that we have no conflict of interest.
- Balic M, Lin H, Young L, Hawes D, Giuliano A, McNamara G, Datar RH, Cote RJ (2006) Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res 12(19):5615–5621. doi: 10.1158/1078-0432.CCR-06-0169 PubMedCrossRefGoogle Scholar
- Ghods AJ, Irvin D, Liu G, Yuan X, Abdulkadir IR, Tunici P, Konda B, Wachsmann-Hogiu S, Black KL, Yu JS (2007) Spheres isolated from 9L gliosarcoma rat cell line possess chemoresistant and aggressive cancer stem-like cells. Stem Cells 25(7):1645–1653. doi: 10.1634/stemcells.2006-0624 PubMedCrossRefGoogle Scholar
- Liu T, Xu F, Du X, Lai D, Zhao Y, Huang Q, Jiang L, Huang W, Cheng W, Liu Z (2010) Establishment and characterization of multi-drug resistant, prostate carcinoma-initiating stem-like cells from human prostate cancer cell lines 22RV1. Mol Cell Biochem 340(1–2):265–273. doi: 10.1007/s11010-010-0426-5 PubMedCrossRefGoogle Scholar
- Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S, Wiggins JF, Bader AG, Fagin R, Brown D, Tang DG (2011) The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med 17(2):211–215. doi: 10.1038/nm.2284 PubMedCrossRefGoogle Scholar
- Olsson E, Honeth G, Bendahl PO, Saal LH, Gruvberger-Saal S, Ringner M, Vallon-Christersson J, Jonsson G, Holm K, Lovgren K, Ferno M, Grabau D, Borg A, Hegardt C (2011) CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers. BMC Cancer 11(1):418. doi: 10.1186/1471-2407-11-418 PubMedCrossRefGoogle Scholar
- Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, Reilly JG, Chandra D, Zhou J, Claypool K, Coghlan L, Tang DG (2006) Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 25(12):1696–1708. doi: 10.1038/sj.onc.1209327 PubMedCrossRefGoogle Scholar
- Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S, Pierotti MA, Daidone MG (2005) Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 65(13):5506–5511. doi: 10.1158/0008-5472.CAN-05-0626 PubMedCrossRefGoogle Scholar
- Wang X, Venugopal C, Manoranjan B, McFarlane N, O’Farrell E, Nolte S, Gunnarsson T, Hollenberg R, Kwiecien J, Northcott P, Taylor MD, Hawkins C, Singh SK (2011) Sonic hedgehog regulates Bmi1 in human medulloblastoma brain tumor-initiating cells. Oncogene. doi: 10.1038/onc.2011.232onc2011232 Google Scholar
- Yu CC, Lo WL, Chen YW, Huang PI, Hsu HS, Tseng LM, Hung SC, Kao SY, Chang CJ, Chiou SH (2011) Bmi-1 regulates snail expression and promotes metastasis ability in head and neck squamous cancer-derived ALDH1 positive cells. J Oncol 2011, art no 609259. doi: 10.1155/2011/609259
- Zen Y, Fujii T, Yoshikawa S, Takamura H, Tani T, Ohta T, Nakanuma Y (2007) Histological and culture studies with respect to ABCG2 expression support the existence of a cancer cell hierarchy in human hepatocellular carcinoma. Am J Pathol 170(5):1750–1762. doi: 10.2353/ajpath.2007.060798 PubMedCrossRefGoogle Scholar
- Zhao C, Chen A, Jamieson CH, Fereshteh M, Abrahamsson A, Blum J, Kwon HY, Kim J, Chute JP, Rizzieri D, Munchhof M, VanArsdale T, Beachy PA, Reya T (2009) Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia. Nature 458(7239):776–779. doi: 10.1038/nature07737 PubMedCrossRefGoogle Scholar