A Role for Laminin-5 in Human Breast Cancer Invasion

Abstract : Extracellular matrix proteins (SCM) play a key role in tissue remodeling and tumor progression. We have shown that matrix metalloproteinase (MMP-2) cleaves Ln-5 and promotes cell migration. We report here that the expression of MMP-2 and the cleavage of Ln-5 correlate with the tissue remodeling of the mammary gland in vivo and in vitro as well. Sex steroids stimulate the development of the gland, with the occurrence of new buds and branches. In this situation Ln-5 was detected in the cleaved form, and MMP-2 concentrated along the mammary epithelial cells penetrating in the fat pad. A remodeling of the mammary gland tissue with a concomitant cleavage of Ln-5 was also observed in cultured mammary gland tissue These results suggest that a cleavage of Ln-5 by MMP-2 might be regulated by sex steroids and that this could contribute to tissue remodeling and cancer metastasis. An alternative possibility is that MTl-MMP could cleave Ln-5, in those cells that do not express MMP-2. We demonstrated that MTl-MMP is also able to promote cell migration via Ln-5 cleavage. Several evidences suggest that this mechanism might be largely diffuse in cancer tissues and the cleavage of Ln-5 could be relevant for tumor progression and metastasis.