TY - JOUR
T1 - Primary versus castration-resistant prostate cancer
T2 - Modeling through novel murine prostate cancer cell line
AU - Daoud, Georges
AU - Monzer, Alissar
AU - Bahmad, Hisham
AU - Chamaa, Farah
AU - Hamdar, Layal
AU - Mouhieddine, Tarek H.
AU - Shayya, Sami
AU - Eid, Assaad
AU - Kobeissy, Firas
AU - Liu, Yen Nien
AU - Abou-Kheir, Wassim
PY - 2016/5/17
Y1 - 2016/5/17
N2 - 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.
AB - 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.
KW - Cancer stem cells
KW - Castration-resistant prostate cancer
KW - Prostate cancer
KW - Pten
KW - TP53
UR - http://www.scopus.com/inward/record.url?scp=84969796294&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84969796294&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.8436
DO - 10.18632/oncotarget.8436
M3 - Article
C2 - 27036046
AN - SCOPUS:84969796294
SN - 1949-2553
VL - 7
SP - 28961
EP - 28975
JO - Oncotarget
JF - Oncotarget
IS - 20
ER -