A mechanism for regulation of melanoma invasion - Ligation of alpha(6)beta(1) integrin by laminin G peptides

被引:103
作者
Nakahara, H
Nomizu, M
Akiyama, SK
Yamada, Y
Yeh, YY
Chen, WT
机构
[1] GEORGETOWN UNIV,MED CTR,LOMBARDI CANC CTR,WASHINGTON,DC 20007
[2] GEORGETOWN UNIV,MED CTR,DEPT CELL BIOL,WASHINGTON,DC 20007
[3] NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892
关键词
D O I
10.1074/jbc.271.44.27221
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Invasion of LOX human melanoma cells involves extracellular matrix (ECM) degradation and formation of cell surface invadopodia. Here we show that the ligation of alpha(6) beta(1) by two peptides derived from the COOH-terminal globular domain of laminin-1 alpha(1) chain (laminin G peptides), designated AG-10 (NPWHSIYITRFG) and AG-32 (TWYKIAFQRNRK), and antibodies against alpha(6) and beta(1) integrins promoted invasiveness. AG-10 and AG-SB inhibited cell adhesion on laminin, and the antibodies blocked cell adhesion on immobilized AG-10 and AG-32, suggesting that the peptides interact primarily with alpha(6) beta(1) integrin. These soluble peptides and integrin antibodies induced invasiveness by causing an 2-3-fold increase in ECM degradation and invadopodial activity independently of adhesion activity of integrins that were prebound to ECM. The induced ECM degradation and invasion was associated with an increased surface expression of the 170-kDa membrane-bound gelatinase, seprase, as well as its intense localization at invadopodia but not at focal adhesions. However, the total expression levels of seprase, gelatinase A and beta(1) integrins were not altered. We suggest that laminin G peptides act on the alpha(6) beta(1) integrin signaling of invasion by stimulating invadopodial activities, which is distinct from their direct effects on cell adhesion on immobilized ECM.
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页码:27221 / 27224
页数:4
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