Identification of a novel function for 67-kDa laminin receptor: increase in laminin degradation rate and release of motility fragments.

Abstract

The 67-kDa laminin receptor (67LR) is a high-affinity laminin-binding protein that is overexpressed on the tumor cell surface in a variety of cancers. We report here that the 67LR molecule also functions in the proteolytic cleavage of laminin-1, a relevant event in basement membrane degradation and tumor dissemination. In the presence of a synthetic peptide (peptide G) corresponding to the 67LR laminin binding site, the rate of laminin-1 degradation by the cysteine proteinase cathepsin B was significantly increased, and a new proteolytic fragment particularly active in in vitro cell migration assays was generated. The YIGSR peptide, corresponding to the 67LR binding site on laminin-1, blocked the peptide G-dependent proteolytic degradation. Our results shed light on the mechanism by which an adhesion receptor such as the 67LR plays a major role in tumor aggressiveness and metastasis.