Abstract Metastatic prostate cancer is the second leading cause of cancer deaths among men in the U.S. Metastasis involves regulators, which involve complex cell signaling processes and our current knowledge on how prostate cancer metastasis develops is still under investigation. If these regulators can be identified and the mechanisms fully elucidated, they can be potential targets for oncologic treatment. CD82 (KAI1), a tetraspanin first identified as a metastasis tumor suppressor in prostate cells is one such regulator involved in the metastatic process. Currently, CD82 downregulation is not only observed in prostate but also in a variety of many invasive epithelial tumors which include tumors of the gastric, colon, cervix, breast, skin, bladder, lung, pancreas, liver, and thyroid. CD82 has been well documented as an inhibitor of cell motility and invasion in cancer cells, with varied inhibitory mechanisms. By introducing CD82 in metastatic cell lines (PC3) that do not express CD82, we have shown CD82 to regulate c-Met, a growth factor receptor, a protooncogene that is over expressed and or over activated in prostate tumors. Overactivation of c-Met promotes cell proliferation, migration and invasion. However, it is still not well understood how exactly CD82 regulates c-Met. Using metastatic prostate cell lines (PC3) and comparing them with PC3 clones generated to express CD82, we are using immunofluorescence, immunoprecipitation, flow cytometry, and western blot techniques to analyze the exact mechanism by which CD82 regulates c-Met. Preliminary data indicate CD82 does not colocalize with CD82, nor does it downregulate c-Met expression on the cell surface. However, CD82 expression seems to cause varied distribution of c-Met in the cell and is currently being investigated. Preliminary indications are that CD151, another tetraspanin may be involved in this regulation. CD151 is a known tumor promoter and has been shown to associate with c-Met. Currently, our lab is exploring the redistribution pattern of c-Met upon CD82 expression as a regulatory mechanism, in addition to exploring the CD82 and CD151 expression dynamics as part of or as alternate mechanism to c-Met regulation. The results observed will provide insights into the role CD82 plays in c-Met regulation as well as it may overall play in tumor progression and metastasis in prostate cancer. Notably, the results may also shed more light on CD82 regulation in other tumors where CD82 downregulation is observed. Citation Format: Suganthi Sridhar, Emily Brandes, Patrick Aller, Eddie Barrie. CD82 regulation of c-Met in metastatic prostate cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2496.