Premium
Evidence of epithelial to mesenchymal transition associated with increased tumorigenic potential in an immortalized normal prostate epithelial cell line
Author(s) -
Marian Calin O.,
Yang Lin,
Zou Ying S.,
Gore Crystal,
Pong ReyChen,
Shay Jerry W.,
Kabbani Wareef,
Hsieh JerTsong,
Raj Ganesh V.
Publication year - 2011
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21278
Subject(s) - matrigel , prostate cancer , cell culture , metastasis , epithelial–mesenchymal transition , cancer research , biology , prostate , pathology , immortalised cell line , nude mouse , mesenchymal stem cell , epithelium , cell , cancer , medicine , angiogenesis , genetics
BACKGROUND The majority of established human prostate cancer cell lines are derived from metastatic lesions and are already tumorigenic in vivo, therefore immortalized normal prostate cell lines may provide a more relevant model to unveil the mechanisms associated with cancer progression and metastasis. METHODS PZ‐HPV‐7, an immortalized human prostate epithelial cell line was used to generate xenograft tumors in mice. A subline designated HPV‐PZ‐7T was subsequently derived from the subrenal capsule xenograft of a nude mouse. These cells were further characterized using karyotyping, immunofluorescence, qRT‐PCR, Western blotting, and three‐dimensional cultures in Matrigel. RESULTS The PZ‐HPV‐7 cell line possesses a typical epithelial morphology, expresses basal cell markers, and is capable of forming web‐like structures with evidence of budding on Matrigel. PZ‐HPV‐7 is non‐tumorigenic in immunocompromised mice by either subcutaneous injection or subrenal grafting. In contrast, the PZ‐HPV‐7T cells, derived from a xenograft tumor induced by co‐inoculation with matrigel using subrenal grafting, possess a mesenchymal phenotype as well as luminal cell markers and are highly tumorigenic and metastatic in nude mice. Functionally and biochemically, the PZ‐HPV‐7T subline appears to have undergone an epithelial‐to‐mesenchymal transition (EMT) from the parental PZ‐HPV‐7 line. CONCLUSION We have developed a novel EMT model using an immortalized normal prostate epithelial cell line and generated a new prostate cancer cell line, PZ‐HPV‐7T, which may represent an excellent system to study mechanisms associated with prostate cancer progression and metastasis. Prostate 71:626–636, 2011. © 2010 Wiley‐Liss, Inc.