Activation of G-proteins with AlF4- induces LFA-I-mediated adhesion of T-cell hybridoma cells to ICAM-1 by signal pathways that differ from phorbol ester- and manganese-induced adhesion

被引:14
作者
Driessens, MHE [1 ]
vanHulten, PEM [1 ]
vanRijthoven, EAM [1 ]
Soede, RDM [1 ]
Roos, E [1 ]
机构
[1] NETHERLANDS CANC INST, DIV CELL BIOL, NL-1066 CX AMSTERDAM, NETHERLANDS
关键词
D O I
10.1006/excr.1996.3463
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
T-cell hybridomas metastasize widely, and the extent of dissemination correlates with invasiveness in fibroblast cultures. Previously, we provided evidence that both metastasis and in vitro invasion require activation of LFA-1, induced by G-protein-transduced signals triggered by as yet unidentified factors. We show here that LFA-P-mediated adhesion of TAM2D2 T-cell hybridoma cells to ICAM-1 can in fact be induced by direct activation of G-proteins using AlF4-, to the same extent as by using PMA or Mn2+. We assessed effects of protein kinase C (PKC), tyrosine kinase (TK), PI3-kinase (PI3K), and phospholipase C (PLC) inhibitors. Both AlF4--induced adhesion and invasion were completely blocked by the TK inhibitor genistein and partially blocked by the PI3K inhibitor wortmannin, but not influenced by PKC inhibitor GF109203X. Downregulation of PKC did not affect invasion or adhesion induced by AlF4- either. In contrast, GF109203X and PKC downregulation blocked PMA-induced adhesion, but genistein and wortmannin had no effect. Invasion and both AlF4- and PMA-induced adhesion were completely blocked by the PLC inhibitor U73122. Mn2+-induced adhesion, which was not or was only partially blocked by the other inhibitors, was delayed by U73122, and spreading of Mn2+-treated cells was completely prevented by U73122. However, PLC activity during adhesion was not detected, We conclude that signals required for invasion and G-protein-induced adhesion are similar and are distinct from PKC-induced adhesion, and that in all eases PLC is likely to be activated, but is probably too local and/or transient to be detected. (C) 1997 Academic Press.
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页码:242 / 250
页数:9
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