Primary versus castration-resistant prostate cancer: modeling through novel murine prostate cancer cell lines
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Georges Daoud1,*, Alissar Monzer1,*, Hisham Bahmad1,*, Farah Chamaa1, Layal Hamdar1, Tarek H. Mouhieddine1, Sami Shayya1, Assaad Eid1, Firas Kobeissy2, Yen-Nien Liu3, Wassim Abou-Kheir1
1Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
2Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
3Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
*These authors contributed equally to this work
Wassim Abou-Kheir, email: [email protected]
Yen-Nien Liu, email: [email protected]
Firas Kobeissy, email: [email protected]
Keywords: prostate cancer, castration-resistant prostate cancer, cancer stem cells, Pten, TP53
Received: September 21, 2015 Accepted: March 04, 2016 Published: March 28, 2016
Cell lines representing the progression of prostate cancer (PC) from an androgen-dependent to an androgen-independent state are scarce. In this study, we used previously characterized prostate luminal epithelial cell line (Plum), under androgen influence, to establish cellular models of PC progression. Cells derived from orthotopic tumors have been isolated to develop an androgen-dependent (PLum-AD) versus an androgen-independent (PLum-AI) model. Upon immunofluorescent, qRT-PCR and Western blot analyses, PLum-AD cells mostly expressed prostate epithelial markers while PLum-AI cells expressed mesenchymal cell markers. Interestingly, both cell lines maintained a population of stem/progenitor cells. Furthermore, our data suggest that both cell lines are tumorigenic; PLum-AD resulted in an adenocarcinoma whereas PLum-AI resulted in a sarcomatoid carcinoma when transplanted subcutaneously in NOD-SCID mice. Finally, gene expression profiles showed enrichment in functions involved in cell migration, apoptosis, as well as neoplasm invasiveness and metastasis in PLum-AI cells. In conclusion, these data suggest that the newly isolated cell lines represent a new in vitro model of androgen-dependent and –independent PC.
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