Integrin alpha6beta1 plays a significant role in the attachment of hepatoma cells to laminin.
OBJECTIVE
Tumor invasion and metastasis consist of a series of complex events. During this process, the ability of tumor cells to adhere to laminin, a major component of basement membranes, is required at various steps. The expression of laminin-binding integrins and the extent of tumor metastasis and progression appear to be related. In hepatocellular carcinoma, increased expression of laminin-binding integrins is observed. However, little is known concerning the possible functional interactions between laminin-binding integrins and laminin. Therefore, we investigated the participation of laminin-binding integrins in the attachment of hepatoma cells to laminin.


METHODS
Human hepatoma cell lines (KIM-1, KYN-1, 2) were used. We investigated the expression of integrin alpha1, alpha2, alpha3, alpha6, beta1, and beta4 subunits on hepatoma cells by immunocytochemical and flow cytometric analysis. Participation of these integrin subunits in the attachment of hepatoma cells to laminin was evaluated by an inhibition of cell adhesion assay.


RESULTS
Integrin alpha1, alpha2, alpha3, alpha6 and beta1 subunits were expressed at the marginal areas of hepatoma cells, while the integrin beta4 subunit was scarcely detected. Laminin promoted the attachment of hepatoma cells in a dose-dependent manner. Although anti-integrin alpha1, alpha2, beta3 and beta4 subunit antibodies did not inhibit cell attachment to laminin, anti-integrin alpha6 and beta1 subunit antibodies inhibited the attachment by 50% or more.


CONCLUSIONS
These findings indicate that integrin alpha6beta1 is very important in the attachment of hepatoma cells to laminin, suggesting the participation of this integrin in metastasis and invasion of hepatoma cells.
Torimura
T
T
Second Department of Medicine and Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Japan.
Ueno
T
T
Kin
M
M
Ogata
R
R
Inuzuka
S
S
Sugawara
H
H
Kurotatsu
R
R
Shimada
M
M
Yano
H
H
Kojiro
M
M
Tanikawa
K
K
Sata
M
M
D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000503:physiopathology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D039121:Integrin alpha6beta1; D016023:Integrins / Q000502:physiology*; D007797:Laminin / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000473:pathology / Q000503:physiopathology*; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D014407:Tumor Cells, Cultured
D039121:Integrin alpha6beta1; D016023:Integrins; D007797:Laminin