The novel monoclonal antibody MH8-4 inhibiting cell motility recognizes integrin alpha 3: inverse of its expression with metastases in colon cancer

The molecular basis of cell motility is obviously highly complex and is con sidered to be controlled by a number of molecular systems including cell ad hesion molecules, their receptors, cytoskeletal components, a junctional un it connecting cytoskeletal components and membrane receptors, and various p eptide growth factors. The possible involvement of proteins at the cell sur face in controlling cell motility has been systematically investigated. Pre viously, we have addressed this question using functional monoclonal antibo dies (MAbs), which inhibit cell motility as probes. In order to further ide ntify cell surface molecules involved in metastasis of gastrointestinal tum ors, the present study utilized an approach based on the selection of a col on cancer cell line RPMI4788, which showed high motility out of a large num ber of human gastrointestinal tumor cell lines. MAb MH8-4 was established a fter immunization of mice with RPMI4788 and selected on the basis of inhibi tion of RPMI4788 cell migration in a transwell penetration assay. MH8-4 inh ibited the phagokinetic tract motility of various cancer cell lines. A cDNA cloning revealed that MH8-4 recognized a specific protein structure, integ rin alpha3. In order to determine whether these experimental results are of relevance with respect to actual human gastrointestinal tumors, we investi gated integrin alpha3 expression in 40 colon cancers with distant metastase s. Our immunohistochemical study showed that in almost 27.5% of the cases, the metastatic tumors had lower integrin alpha3 levels than their correspon ding primary tumors. Moreover, there were no primary tumors with lower inte grin alpha3 expression than their corresponding metastatic tumors. Our data suggest that low integrin alpha3 expression may be associated with the met astatic potential of certain colon cancers.