Title

Involvement of HGF/SF–Met Signaling in Prostate Adenocarcinoma Cells: Evidence for Alternative Mechanisms Leading to a Metastatic Phenotype in Pr-14c

Document Type

Article

Publication Date

7-1-2005

Abstract

BACKGROUND

Hepatocyte growth factor/scatter factor (HGF/SF) facilitates intercellular communication between the epithelial carcinoma and its surrounding stromal tissue during metastatic invasion through interaction with its proto-oncogenic receptor, Met, found on carcinoma cells. This study utilizes the C3(1)/Tag transgenic mouse prostate cancer cell line model in an attempt to characterize the interaction between HGF/SF and Met on the metastatic potential of prostate cancer.

METHODS

Exogenous HGF was supplied to the prostate adenocarcinoma cell line (Pr-14) and metastatic cell line (Pr-14c) to evaluate mitogenicity by proliferation assays, morphological characteristics on an extracellular matrix substrate, and motogenic properties using the scatter assay, invasion chambers, and zymogram studies to analyze secretory enzymes produced by the cell lines.

RESULTS

RNA and protein analyses show that the cell lines express similar amounts of Met. Pr-14 cells have an increased growth rate following HGF/SF treatment, whereas the metastatic Pr-14c cells show little change. Morphological studies of Pr-14c cells on extracellular matrix demonstrate negligible changes when compared to the tubular formation of Pr-14 cells after HGF/SF stimulation. Motility studies of the metastatic cells following HGF/SF treatment reveal a potentially faulty signaling pathway downstream of Met activation in the metastatic prostate cells.

CONCLUSIONS

Our studies suggest that proliferation, invasion, and cell morphological characteristics may be induced independently from the HGF/SF-Met pathway in C3(1)/Tag metastatic prostate cancer cells.