New proteins binding specifically to the ED-b fibronectin domain, are cell adhesion and proliferation mediators useful e.g. in screening tests

摘要

A new protein (I) binds specifically to the EDb fibronectin domain (EDbFD) (this binding being inhibited by a polypeptide (II)); is specifically expressed or activated in endothelial cells, stromal cells of a tumor and tumor cells; and has an apparent molecular weight of 120-130 kDa for the light chain and 150-160 kDa for the heavy chain (as determined by SDS-polyacrylamide gel electrophoresis). Independent claims are also included for: (1) proteins (I') which, by binding specifically to the EDbFD: (i) mediate the adhesion of endothelial, tumor stroma and tumor cells; (ii) induce proliferation of endothelial cells; or (iii) induce the proliferation, migration and differentiation of endothelial cells in a collagen matrix; (2) proteins (I'') which bind specifically to the EDbFD, induce specific transduction pathways and induce at least one gene encoding a protein selected from focal adhesion kinase, CD6-ligand (ALCAM), the alpha -chain or the vitronectin receptor, the integrated alpha 8 subunit and a precursor for follistatin-related protein; (3) antibodies which bind to (I)/(I') or to a protein (II) having one of four aminoacid sequences (three having 15 aminoacids and one having 91 aminoacid; given in the specification as SEQ ID NO: 1-4); (4) cells expressing a protein (I)/(I') or an antibody (3); and (5) phages expressing an antibody (3).