| Tumor cells interact with basement membrane collagen at the site of extravasation through distinct cellular receptors, including the alpha2beta 1 and alpha3beta1 integrins. These receptors are known to be differentially expressed in metastatic tumors, relative to the normal cells, depending on tumor type and stage of progression. The binding sites within type IV collagen for the alpha2beta1 and alpha3beta1 integrins have been identified. Since both of the integrin-specific sequences possess at least one glycosylated Hyl residue, we questioned whether glycosylation could modulate integrin binding. Triple-helical peptides with and without Lys substituted by glycosylated Hyl for Lys543 and Lys540 from the human alpha1(IV)531-543 gene sequence (alpha3beta1 integrin-specific) and Lys393 from the human alpha1(IV)382-393 gene sequence (alpha2beta1 integrin-specific) were synthesized and utilized in the present study. Cellular response to these triple helical ligands was tested with a primary melanoma cell line, WM-115, and three highly metastatic melanoma cell lines, WM-266-4, M14... |
