The role of P13-kinase on melanoma cell adhesion and migration

Abstract

Integrins are responsible for anchoring cells to the extracellular matrix and also can initiate intracellular signal pathways. The interaction between integrins and the extracellular matrix results in activation of PKC, PTKs, p21Ras, MAPK and PI3-kinase. The $\alpha$4$\beta$1 integrins are expressed mainly on haematopoietic cells and also appear on several tumour types. The adhesion of $\alpha$4$\beta$1 to VCAM-1 is an essential step for lymphocyte extravasation during the inflammatory response. Furthermore, the interaction of $\alpha$4$\beta$1, expressed on tumour cells, with VCAM-1, might have a role in tumour cell extravasation. We examined the role of PI3-kinase activation in a$\alpha$4$\beta$1-mediated melanoma cell adhesion and migration. Inhibition of PI3-kinase did not have any effect on cell adhesion. However, the migration of HMB2-$\alpha$4 and DX3 cells on fibronectin, but not VUP-$\alpha$4, was inhibited by PI3-kinase inhibitor. $\alpha$v$\beta$3-mediated migration in VUP cells which had been transfected with $\beta$3 cDNA to create expression of the $\alpha$v$\beta$3, did not involve PI3-kinas e activity, suggesting that this was not the case. On the other hand, VUP-$\alpha$4 cells were found not to express p110$\alpha$, a specific form of PI3-kinase, which may be involved in melanoma migration, whereas the HMB2-$\alpha$4 cells expressed this isoform.

Integrins are responsible for anchoring cells to the extracellular matrix and also can initiate intracellular signal pathways. The interaction between integrins and the extracellular matrix results in activation of PKC, PTKs, p21Ras, MAPK and PI3-kinase. The $\alpha$4$\beta$1 integrins are expressed mainly on haematopoietic cells and also appear on several tumour types. The adhesion of $\alpha$4$\beta$1 to VCAM-1 is an essential step for lymphocyte extravasation during the inflammatory response. Furthermore, the interaction of $\alpha$4$\beta$1, expressed on tumour cells, with VCAM-1, might have a role in tumour cell extravasation. We examined the role of PI3-kinase activation in a$\alpha$4$\beta$1-mediated melanoma cell adhesion and migration. Inhibition of PI3-kinase did not have any effect on cell adhesion. However, the migration of HMB2-$\alpha$4 and DX3 cells on fibronectin, but not VUP-$\alpha$4, was inhibited by PI3-kinase inhibitor. $\alpha$v$\beta$3-mediated migration in VUP cells which had been transfected with $\beta$3 cDNA to create expression of the $\alpha$v$\beta$3, did not involve PI3-kinas e activity, suggesting that this was not the case. On the other hand, VUP-$\alpha$4 cells were found not to express p110$\alpha$, a specific form of PI3-kinase, which may be involved in melanoma migration, whereas the HMB2-$\alpha$4 cells expressed this isoform.