The overall goal of the research has been to identify and characterize biochemical mechanisms involved in the interaction of metastatic tumor cells with the extracellular matrix. A major objective has been to analyze the events which take place at the interface between the tumor cell and the basement membrane during attachment. Accomplishments 1. Laminin, a glycoprotein of basement membranes, was shown to play a major role in metastatic tumor cell attachment. 2. The cell surface laminin receptor was purified and partially sequenced. 3. Monoclonal antibodies and polyclonal antibodies were prepared against the human breast cancer laminin receptor. These antibodies have provided new information about the distribution and function of the receptor. The antibodies were also used to screen a cDNA expression library to isolate a putative cDNA clone from the human gene coding for the receptor. 4. The binding domain on the receptor and the ligand were identified. Additional functional domains were located on the ligand and a model of the attachment interface was developed. 5. A fragment of the laminin ligand was produced which blocks the receptor and markedly inhibits or abolishes hematogenous metastases in a nontoxic fashion in animal models.
