A specific sequence of the noncollagenous domain of the alpha 3(IV) chain of type IV collagen inhibits expression and activation of matrix metalloproteinases by tumor cells

The invasive properties of melanoma cells correlate with the expression of matrix metalloproteinases (MMPs) and their physiological modulators (tissue inhibitors of metalloproteinase and membrane-type MMPs) and with that of t he alpha V beta 3 integrin, We investigated the effect of anterior lens cap sule type IV collagen and of the alpha 3(IV) collagen chain on the invasive properties of various tumor cell lines (HT-144 melanoma cells, HT-1080 fib rosarcoma cells). We demonstrated that anterior lens capsule type TV collag en or specifically the synthetic peptide alpha 3(IV) 185-203 inhibited both the migration of melanoma or fibrosarcoma cells as well as the activation of membrane-bound MMP-2 by decreasing the expressions of MT1-MMP and the be ta 3 integrin subunit.