Transforming growth factor-beta-inducible gene-h3 (beta(ig)-h3) promotes cell adhesion of human astrocytoma cells in vitro: implication of alpha6beta4 integrin.
Beta(ig)-h3 is a secretory protein that is induced by transforming growth factor (TGF)-beta. We have recently found that beta(ig)-h3 expression is induced in cultured astrocytes by TGF-beta1 and in rat cerebral cortex by stab wound. The purpose of this study was to examine the effect of the secreted beta(ig)-h3 on cell adhesion of astrocytes and the underlying mechanisms. When U87 human astrocytoma cells were seeded on dishes coated with recombinant beta(ig)-h3, cell adhesion was significantly enhanced. Blocking experiments using various antibodies to the integrin subunit suggested alpha6beta4 integrin could be involved in the beta(ig)-h3-mediated astrocyte cell adhesion. Cell adhesion to beta(ig)-h3 substrate was substantially blocked by preincubation with the inhibitor to the src kinase. When cells were plated on beta(ig)-h3-coated dishes, tyrosine phosphorylation of focal adhesion kinase was prominently increased within 20 min in a beta4 integrin-dependent manner. The results suggest that alpha6beta4 integrin-mediated interactions of astrocytes with beta(ig)-h3 transduce intracellular signals through the focal adhesion proteins, which may regulate certain aspects of astrocyte response to brain injury.
Kim
Mi-Ok
MO
Graduate School of East-West Medical Science, Kyung Hee University, 1 Seochun, Yong-In 449-701, South Korea.
Yun
Su-Jin
SJ
Kim
In-San
IS
Sohn
Seonghyang
S
Lee
Eunjoo-H
EH
D001254:Astrocytoma / Q000378:metabolism* / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins; D006801:Humans; D039121:Integrin alpha6beta1 / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000008:administration & dosage / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016212:Transforming Growth Factor beta; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000378:metabolism; D000099222:betaIG-H3 Protein
D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D039121:Integrin alpha6beta1; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D019061:src-Family Kinases; D000099222:betaIG-H3 Protein