Cancer researchers are focusing their efforts on identifying central pathways that trigger or enhance the invasiveness of tumor cells. One such target is EMMPRIN (Extracellular Matrix Metalloproteinase Inducer). It has been shown that EMMPRIN expression is linked to various cell signaling pathways that lead to an increase in tumor cell vascularization. Researchers are focusing efforts on elucidating the role of EMMPRIN in a number of disorders including cancer, arthritis, tissue repair and numerous inflammation-dependent diseases. DESCRIPTION/DETAILS Basigin is a member of the immunoglobulin superfamily thatis also known as EMMPRIN. Human basigin is expressed as two differentiallyspliced isoforms encoded by a single gene found on chromosome, renamedrespectively as basigin-1 and basigin-2. Attempts to demonstrate specifichemophilic on separate cells, or between soluble forms of recombinant basiginusing surface Plasmon resonance have not been successful, suggesting thatbasigin-2 cannot function as a receptor for itself. In order to identify possible receptors for soluble basiginligand, an affinity purification approach was employed. This approach resulted inthe labeling of several potential interacting proteins, and MALDI MS/MSsequencing of one of these proteins identified a novel isoform of human basigin(basigin-3).
Immunoprecipitation studies using cell fractions revealed thatrBSG interacts with basigin-2 at the cell membrane, and subsequently interactswith the basigin-3 isoform within the cell. Small-interfering RNA (siRNA)knockdown of basigin-2 protein reduced, but did not eliminate, rBSG-mediatedERK activation in HESCs, suggesting that additional cell surface receptors forsoluble basigin may exist. Taken together, these results support the hypothesisthat basigin-2 can function as a receptor for soluble basigin and demonstratethat the hemophilic interactions between basigin proteins are not dependentupon glycosylation of the basigin ligand. It has also been shown that soluble EMMPRIN binds tomembrane-bound EMMPRIN and the bound complex is internalized presenting apotential means to deliver therapeutic compounds to the cell in a highlytargeted manner. A therapeutic scheme isproposed that aims to design EMMPRIN-conjugates designed to deliver cancertherapeutics in a targeted fashion.
Applications
Conjugation oftherapeutics to EMMPRIN increases specificity and targets cancers cells cancer (skin, bladder,breast); other inflammatory diseases (arthritis, endometriosis); Upregulationof inflammatory response.
Benefits
It is possible to design therapeutic agents directed toward human basigin. Possible therapeutic scheme to block tumor progressionor inflammation.