Role of HGF/C-met system in invasion and metastasis of oral squamous cell carcinoma cells in vitro and its clinical significance

Daisuke Uchida, Hitoshi Kawamata, Fumie Omotehara, Koh Ichi Nakashiro, Tetsuo Kimura-Yanagawa, Satoshi Hino, Nasima Mila Begum, Mohammad O. Hoque, Hideo Yoshida, Mitsunobu Sato, Takahiro Fujimori

Research output: Contribution to journalArticlepeer-review

Abstract

We examined the role of the hepatocyte growth factor (HGF)/c-met system on invasion and metastasis of oral squamous cell carcinoma (SCC) cells. In monolayer culture, exogenous HGF marginally affected the growth of oral SCC cells (BHY, HN, IH) and human gingival epithelial cells (GE). In type I collagen matrix, however, HGF significantly enhanced the invasive growth of the cancer cells (p < 0.05). We detected the expression of c-met (HGF receptor) mRNA in all of the cancer cells, but not in human gingival fibroblasts (GF). Oral SCC cells did not secret HGF protein into the medium, but GF secreted a large amount of HGF protein (15 ng/ml). Furthermore, HGF markedly enhanced the migration of cancer cells in a Transwell invasion chamber. Then, we examined the serum levels of HGF in oral SCC patients, or HGF concentrations in oral cancer tissues. Serum levels of HGF in the patients were significantly higher than those in healthy volunteers (p < 0.05). After initial treatment, all of the tumor-free survivors showed a marked decline in the serum HGF levels. Furthermore, HGF concentrations in metastatic cancer tissues were significantly higher than those of nonmetastatic cancer tissues and normal gingiva (p < 0.01). These results suggest that HGF plays an important role in invasion and metastasis of oral SCC cells as a paracrine factor, and an elevated HGF level in the cancer tissue can be a predictive marker for metastasis formation in patients with oral SCC.

Original languageEnglish (US)
Pages (from-to)489-496
Number of pages8
JournalInternational Journal of Cancer
Volume93
Issue number4
DOIs
StatePublished - Aug 15 2001
Externally publishedYes

Keywords

  • HGF
  • Metastasis
  • Oral SCC
  • c-met

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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