340 Role of adhesion receptors in tumour spread

Abstract

Since tumour spread involves numerous cell to cell and cell to matrix interactions it is expected that alterations in expression of cell adhesion receptors will play a significant role in modulating metastasis. Our interests have focused primarily upon the adhesion receptors involved in regulating the spread of malignant melanoma. Immunocytochemistry of clinical specimens has shown that the <i>α</i>₄<i>β</i>₁ integrin is expressed in melanoma but that this expression is restricted to metastases. We have identified two <i>α</i>₄ deficient melanoma cell lines, HMB2 and VUP, which have had <i>α</i>₄<i>β</i>₁ expression reconstituted by infection with retroviruses carrying <i>α</i>₄ cDNA. Such reconstituted VUP and HMB2 lines are able to bind to VCAM-1, an inducible endothelial cell adhesion molecule expressed on the surface of activated endothelium, and that such binding is inhibited with an <i>α</i>₄ blocking antibody HP21. Binding of anti <i>α</i>₄ antibody to the <i>α</i>₄ expressing melanoma cell lines results in the induction of second messenger molecules, such as a calcium spike, and changes not only in adhesive but also in a migratory capacity. Thus, migration on VCAM-1 by human melanoma cells is <i>α</i>₄<i>β</i>₁ dependent suggesting that adhesion molecules expressed during tumor progression may play substantial roles in different steps of the metastatic process.