Evidence of epithelial to mesenchymal transition associated with increased tumorigenic potential in an immortalized normal prostate epithelial cell line

Calin O. Marian, Lin Yang, Ying S. Zou, Crystal Gore, Rey Chen Pong, Jerry W. Shay, Wareef Kabbani, Jer Tsong Hsieh, Ganesh V. Raj

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)626-636
Number of pages11
JournalProstate
Volume71
Issue number6
DOIs
StatePublished - May 1 2011

Keywords

  • metastasis
  • prostate cancer
  • xenografts

ASJC Scopus subject areas

  • Oncology
  • Urology

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