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Erschienen in: Journal of Cancer Research and Clinical Oncology 4/2012

01.04.2012 | Original Paper

Tumorspheres derived from prostate cancer cells possess chemoresistant and cancer stem cell properties

verfasst von: Linlin Zhang, Min Jiao, Lei Li, Dapeng Wu, Kaijie Wu, Xiang Li, Guodong Zhu, Qiang Dang, Xinyang Wang, Jer-Tsong Hsieh, Dalin He

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 4/2012

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.
Literatur
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
Zurück zum Zitat Bruggeman SW, Hulsman D, Tanger E, Buckle T, Blom M, Zevenhoven J, van Tellingen O, van Lohuizen M (2007) Bmi1 controls tumor development in an Ink4a/Arf-independent manner in a mouse model for glioma. Cancer Cell 12(4):328–341. doi:10.1016/j.ccr.2007.08.032 PubMedCrossRef Bruggeman SW, Hulsman D, Tanger E, Buckle T, Blom M, Zevenhoven J, van Tellingen O, van Lohuizen M (2007) Bmi1 controls tumor development in an Ink4a/Arf-independent manner in a mouse model for glioma. Cancer Cell 12(4):328–341. doi:10.​1016/​j.​ccr.​2007.​08.​032 PubMedCrossRef
Zurück zum Zitat Cao L, Zhou Y, Zhai B, Liao J, Xu W, Zhang R, Li J, Zhang Y, Chen L, Qian H, Wu M, Yin Z (2011b) Sphere-forming cell subpopulations with cancer stem cell properties in human hepatoma cell lines. BMC Gastroenterol 11:71. doi:10.1186/1471-230X-11-71 PubMedCrossRef Cao L, Zhou Y, Zhai B, Liao J, Xu W, Zhang R, Li J, Zhang Y, Chen L, Qian H, Wu M, Yin Z (2011b) Sphere-forming cell subpopulations with cancer stem cell properties in human hepatoma cell lines. BMC Gastroenterol 11:71. doi:10.​1186/​1471-230X-11-71 PubMedCrossRef
Zurück zum Zitat Fujii H, Honoki K, Tsujiuchi T, Kido A, Yoshitani K, Takakura Y (2009) Sphere-forming stem-like cell populations with drug resistance in human sarcoma cell lines. Int J Oncol 34(5):1381–1386PubMed Fujii H, Honoki K, Tsujiuchi T, Kido A, Yoshitani K, Takakura Y (2009) Sphere-forming stem-like cell populations with drug resistance in human sarcoma cell lines. Int J Oncol 34(5):1381–1386PubMed
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
Zurück zum Zitat Kim M, Turnquist H, Jackson J, Sgagias M, Yan Y, Gong M, Dean M, Sharp JG, Cowan K (2002) The multidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst 33342 and is overexpressed in hematopoietic stem cells. Clin Cancer Res 8(1):22–28PubMed Kim M, Turnquist H, Jackson J, Sgagias M, Yan Y, Gong M, Dean M, Sharp JG, Cowan K (2002) The multidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst 33342 and is overexpressed in hematopoietic stem cells. Clin Cancer Res 8(1):22–28PubMed
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
Zurück zum Zitat Marhaba R, Klingbeil P, Nuebel T, Nazarenko I, Buechler MW, Zoeller M (2008) CD44 and EpCAM: cancer-initiating cell markers. Curr Mol Med 8(8):784–804PubMedCrossRef Marhaba R, Klingbeil P, Nuebel T, Nazarenko I, Buechler MW, Zoeller M (2008) CD44 and EpCAM: cancer-initiating cell markers. Curr Mol Med 8(8):784–804PubMedCrossRef
Zurück zum Zitat Marshall GP 2nd, Reynolds BA, Laywell ED (2007) Using the neurosphere assay to quantify neural stem cells in vivo. Curr Pharm Biotechnol 8(3):141–145PubMedCrossRef Marshall GP 2nd, Reynolds BA, Laywell ED (2007) Using the neurosphere assay to quantify neural stem cells in vivo. Curr Pharm Biotechnol 8(3):141–145PubMedCrossRef
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
Zurück zum Zitat Rappa G, Mercapide J, Anzanello F, Prasmickaite L, Xi Y, Ju J, Fodstad O, Lorico A (2008) Growth of cancer cell lines under stem cell-like conditions has the potential to unveil therapeutic targets. Exp Cell Res 314(10):2110–2122. doi:10.1016/j.yexcr.2008.03.008 PubMedCrossRef Rappa G, Mercapide J, Anzanello F, Prasmickaite L, Xi Y, Ju J, Fodstad O, Lorico A (2008) Growth of cancer cell lines under stem cell-like conditions has the potential to unveil therapeutic targets. Exp Cell Res 314(10):2110–2122. doi:10.​1016/​j.​yexcr.​2008.​03.​008 PubMedCrossRef
Zurück zum Zitat Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63(18):5821–5828PubMed Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63(18):5821–5828PubMed
Zurück zum Zitat Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432(7015):396–401. doi:10.1038/nature03128 PubMedCrossRef Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432(7015):396–401. doi:10.​1038/​nature03128 PubMedCrossRef
Zurück zum Zitat 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 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
Zurück zum Zitat 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 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
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
Zurück zum Zitat 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 PubMedCrossRef 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 PubMedCrossRef
Metadaten
Titel
Tumorspheres derived from prostate cancer cells possess chemoresistant and cancer stem cell properties
verfasst von
Linlin Zhang
Min Jiao
Lei Li
Dapeng Wu
Kaijie Wu
Xiang Li
Guodong Zhu
Qiang Dang
Xinyang Wang
Jer-Tsong Hsieh
Dalin He
Publikationsdatum
01.04.2012
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 4/2012
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-011-1146-2

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