Journal Article

Hepatocyte growth factor is an invasion/migration factor of rat urothelial carcinoma cells <i>in vitro</i>

Tetsuya Tamatani, Kazunori Hattori, Anand Iyer, Kanako Tamatani and Ryoichi Oyasu

in Carcinogenesis

Volume 20, issue 6, pages 957-962
Published in print June 1999 | ISSN: 0143-3334
Published online June 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.6.957
Hepatocyte growth factor is an invasion/migration factor of rat urothelial carcinoma cells in vitro

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Hepatocyte growth factor (HGF) plays an important role in the growth, progression and angiogenesis of various tumors. It is reported that patients with urinary bladder cancer have elevated levels of HGF in urine and that bladder cancer tissue contains an increased amount of HGF. Thus, the data suggest a functional role of HGF in urinary bladder cancer. We evaluated the mechanistic role of HGF in urinary bladder carcinoma in vitro using the rat urothelial cell lines MYP3 (anchorage-dependent and non-tumorigenic in athymic nude mice), LMC19, MYU3L, T6 and AS-HTB1 (anchorage-independent and tumorigenic). The HGF receptor c-met was expressed by all of the cell lines, as determined by northern blot. In MYP3 cells, HGF strongly stimulated anchorage-dependent growth, but not migration, invasion or secretion of matrix metalloproteinases (MMPs). In LMC19, T6 and AS-HTB1 cells, HGF stimulated migration, invasion and secretion of MMPs. Anchorage-dependent growth stimulation was limited to AS-HTB1 cells. MYU3L cells were refractory to HGF in both growth and invasion assays. However, a neutralizing antibody and an anti-sense oligonucleotide to HGF partially inhibited the growth only of MYU3L cells, the finding being indicative of an autocrine stimulatory mechanism. HGF mRNA expression and protein synthesis were induced in bladder stromal cells by the conditioned medium of carcinoma cell lines, and IL-1β and basic fibroblast growth factor were identified as cancer cell-derived HGF-releasing factors. These results suggest that HGF acts as a mitogen in a non-tumorigenic cell line, whereas in tumorigenic cell lines it acts as an invasion and migration factor by either a paracrine or an autocrine mechanism.

Keywords: bFGF, basic fibroblast growth factor; CM, conditioned medium; GAPDH, glyceraldehyde-3-phosphate-dehydrogenase; HGF, hepatocyte growth factor; MMPs, matrix metalloproteinases; MNU, N-methyl-N-nitrosourea; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; PDGF, platelet-derived growth factor.

Journal Article.  5381 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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