title: Hepatocyte growth factor enhances adhesion of breast cancer cells to endothelial cells in vitro through up-regulation of CD44.
abstract: For cancer metastasis, tumor cells present in the circulation must first adhere to the endothelium. Integrins play a central role in leukocyte adhesion to the endothelium and subsequent migration into tissues. The majority of tumor cells derived from solid cancers, including breast cancer, do not express integrins. We investigated the mechanisms of adhesion and transendothelial migration of cancer cells using breast carcinoma cell lines. Our results showed the following features of breast cancer cells: (1) HGF stimulated breast cancer cells by up-regulating CD44 expression in a concentration-dependent manner. (2) the maximum level of HGF-induced CD44 up-regulation on breast cancer cell lines occurred within 3 h. (3) HGF-induced up-regulation of CD44 was mediated by the tyrosine kinase signaling pathway. (4) HGF induced CD44-mediated adhesion of tumor cell lines to bone marrow-derived endothelial cells. (5) HGF did not change rolling of breast cancer cell lines on bone marrow-derived endothelial cells, but enhanced firm adhesion of cancer cells on endothelial cells under shear stress conditions. (6) HGF increased transendothelial migration of cancer cells. Our results indicate that HGF stimulates CD44-mediated adhesion of breast cancer cells to bone marrow-derived endothelial cells, which subsequently results in transendothelial migration of tumor cells. These results suggest that CD44 may confer the metastatic properties of breast cancer cells and, therefore, could be used as a target in future molecular cancer therapy.
authors.affiliation: The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health-Japan, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu 807-8555, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Mine
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujisaki
authors.forename: Chie
authors.initials: C
authors.lastname: Kawahara
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tabata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iida
authors.forename: Manabu
authors.initials: M
authors.lastname: Yasuda
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yoneda
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000187:drug effects* / Q000502:physiology; D007700:Kinetics; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018960:Hyaluronan Receptors; D017228:Hepatocyte Growth Factor