Primary versus castration-resistant prostate cancer: modeling through novel murine prostate cancer cell lines

// Georges Daoud 1, * , Alissar Monzer 1, * , Hisham Bahmad 1, * , Farah Chamaa 1 , Layal Hamdar 1 , Tarek H. Mouhieddine 1 , Sami Shayya 1 , Assaad Eid 1 , Firas Kobeissy 2 , Yen-Nien Liu 3 , Wassim Abou-Kheir 1 1 Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon 2 Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon 3 Graduate 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 Correspondence to: Wassim Abou-Kheir, email: wa12@aub.edu.lb Yen-Nien Liu, email: liuy@tmu.edu.tw Firas Kobeissy, email: fk02@aub.edu.lb Keywords: prostate cancer, castration-resistant prostate cancer, cancer stem cells, Pten, TP53 Received: September 21, 2015 Accepted: March 04, 2016 Published: March 28, 2016 ABSTRACT 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.