title: 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.
authors.affiliation: Molecular Targeting Unit, Department of Experimental Oncology, Istituto Nazionale Tumori, 20133 Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Ardini
authors.forename: Barbara
authors.initials: B
authors.lastname: Sporchia
authors.forename: Loredano
authors.initials: L
authors.lastname: Pollegioni
authors.forename: Michele
authors.initials: M
authors.lastname: Modugno
authors.forename: Cristina
authors.initials: C
authors.lastname: Ghirelli
authors.forename: Fabio
authors.initials: F
authors.lastname: Castiglioni
authors.forename: Elda
authors.initials: E
authors.lastname: Tagliabue
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ménard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D002455:Cell Division; D002465:Cell Movement; D005260:Female; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009369:Neoplasms / Q000473:pathology*; D017474:Receptors, Laminin / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D007797:Laminin; D017474:Receptors, Laminin