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Regulation of lnvasive Potential of Human Prostate Cancer Cell Lines by Hepatocyte Growth Factor
Authors:Kenji Nishimura  Masaya Kitamura  Shingo Takada  Norio Nonomura  Akira Tsujimura  Kiyomi Matsumiya  Tsuneharu Miki  Kunio Matsumoto  Akihiko Okuyama
Institution:Department of Urology, Biomedical Research Center, Osaka University Medical School, Suita, Japan;Division of Biochemistry, Biomedical Research Center, Osaka University Medical School, Suita, Japan
Abstract:Background: The growth and progression of prostate cancer depends on the stromal-epithelial interaction which is under paracrine control. Hepatocyte growth factor (HGF), produced by mesenchymal cells, is a multifunctional growth factor stimulating the movement and growth of epithelial cells including cancer cells. We therefore assessed the relationship between the invasive potential of prostate cancer and HGF in vitro.
Methods: Three human prostate cancer cell lines were used including PC-3 and DU145 (androgenindependent), and LNCaP (androgen-dependent). We studied the expression of the HCF receptor c-met proto-oncogene (c-met) by Western blotanalysis, and alsodetermined theeffectsof HGF on cell scattering, and the mechanisms of invasion and proliferation, by microscopic observation, the matrigel invasion chamber assay, and the MTT assay.
Results: c-met was detected in PC-3 and DU145 cells, but not in the LNCaP cells. There was increased cell motility in the scatter assay and an increased cell invasive potential in the matrigel invasion chamber assay by stimulation with HGF only with DU145 cells.
Conclusion: HGF plays an important role in the invasion and metastasis of the DU145 cell line through a paracrine mechanism mediated by the c-metreceptor. In the PC-3 cell line, the lack of downstream signal transduction after the c-met receptor is suggested.
Keywords:hepatocyte growth factor  c-met  prostate cancer  invasion  matrigel  scatter
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