The interaction of the tumor cell with its extracellular matrix may play an important role in determining its metastatic and invasive properties. To better understand the protein components that make up the extracellular matrix, their regulation, and how they interact with the tumor cell, we have constructed, isolated, and characterized molecular clones of a high affinity 67 kilodalton laminin receptor, and a newly identified 31 kilodalton laminin binding protein. Laminin is a high molecular weight glycoprotein specifically associated with basement membranes. The high affinity 67 kilodalton laminin receptor is a cell surface protein to which laminin binds. We have previously isolated cDNA clones of the human and murine laminin receptor, and have predicted the entire primary Structure of the receptor. Antibodies to specific peptides deduced from the cDNA clones have been used to identify a potential transmembrane domain as well as the ligand binding domain of the receptor. Furthermore, a synthetic peptide successfully inhibited tumor cell attachment to endothelium, thus blocking a key step in the metastatic cascade. The laminin receptor is induced by exposure of cancer cells to extracellular attachment proteins such as laminin and fibronectin, suggesting that as tumor cells are exposed to the extracellular environment they synthesize receptors required for migration and invasion through the connective tissue. Multiple genes for the laminin receptor have been detected, including pseudogenes. The variable expression of this multicopy gene family is under investigation in normal and metastatic tissues. Another laminin binding protein with an approximate molecular weight of 31 kilodaltons was identified in human melanoma cells. Partial protein sequence showed homology with a previously identified carbohydrate binding protein. Polymerase chain reaction technology was used to obtain a partial cDNA clone of this alternate laminin binding protein. Its expression in a variety of carcinoma-derived lines is different from that of the previously identified high affinity laminin receptor.
