title: Basigin-2 is a cell surface receptor for soluble basigin ligand.
abstract: The metastatic spread of a tumor is dependent upon the ability of the tumor to stimulate surrounding stromal cells to express enzymes required for tissue remodeling. The immunoglobulin superfamily protein basigin (EMMPRIN/CD147) is a cell surface glycoprotein expressed by tumor cells that stimulates matrix metalloproteinase and vascular endothelial growth factor expression in stromal cells. The ability of basigin to stimulate expression of molecules involved in tissue remodeling and angiogenesis makes basigin a potential target for the development of strategies to block metastasis. However, the identity of the cell surface receptor for basigin remains controversial. The goal of this study was to determine the identity of the receptor for basigin. Using a novel recombinant basigin protein (rBSG) corresponding to the extracellular domain of basigin, it was demonstrated that the native, nonglycosylated rBSG protein forms dimers in solution. Furthermore, rBSG binds to the surface of uterine fibroblasts, activates the ERK1/2 signaling pathway, and induces expression of matrix metalloproteinases 1, 2, and 3. Proteins that interact with rBSG were isolated using a biotin label transfer technique and sequenced by matrix-assisted laser desorption ionization tandem mass spectrophotometry. The results demonstrate that rBSG interacts with basigin expressed on the surface of fibroblasts and is subsequently internalized. During internalization, rBSG associates with a novel form of human basigin (basigin-3). It was concluded that cell surface basigin functions as a membrane receptor for soluble basigin and this homophilic interaction is not dependent upon glycosylation of the basigin ligand.
authors.affiliation: Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. rbelton@uiuc.edu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Belton
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Fernando S
authors.initials: FS
authors.lastname: Mesquita
authors.forename: Romana A
authors.initials: RA
authors.lastname: Nowak
mesh_terms: D000595:Amino Acid Sequence; D051926:Basigin / Q000378:metabolism / Q000502:physiology*; D001710:Biotin / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism*; D019281:Dimerization; D005347:Fibroblasts / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: C497886:BSG protein, human; D008024:Ligands; D051926:Basigin; D001710:Biotin