title: Role of HGF/c-met system in invasion and metastasis of oral squamous cell carcinoma cells in vitro and its clinical significance.
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 non-metastatic 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.
authors.affiliation: Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Tokushima, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Uchida
authors.forename: H
authors.initials: H
authors.lastname: Kawamata
authors.forename: F
authors.initials: F
authors.lastname: Omotehara
authors.lastname: Nakashiro Ki
authors.forename: T
authors.initials: T
authors.lastname: Kimura-Yanagawa
authors.forename: S
authors.initials: S
authors.lastname: Hino
authors.forename: N M
authors.initials: NM
authors.lastname: Begum
authors.forename: M O
authors.initials: MO
authors.lastname: Hoque
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Fujimori
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met