CD63: A Tissue Inhibitor of Metalloproteinase

Hyeong-Reh Choi Kim, Ph.D
Department of Pathology, Wayne State University School of Medicine
P30ES006639

Metalloproteinases are a family of enzymes with a calcium or zinc ion bound to their active sites. They play an important role in a variety of biological functions including tumor metastasis, embryonic development, wound healing, etc. Previously, it was thought that matrix metalloproteinase inhibitors, such as the drug Marimastat, could counteract the metastatic properties of metalloproteinases. However clinical results have been inconclusive. Tissue inhibitors of the enzyme metalloproteinase-1 (TIMP-1) suppressed cancer metastasis; however, clinical studies linked increased TIMP-1 expression with poor prognosis in certain malignancies, including metastatic breast cancer. This NIEHS-supported research team addressed the issue by investigating the role of TIMP-1 during breast cancer progression.

Dr. Hyeong­Reh Choi Kim’s laboratory was one of the first research teams to report TIMP­1 as an inhibitor of apoptosis. Since this discovery, many investigators have suggested TIMP­1 regulates cell survival through its interaction with an unknown cell surface receptor. In their current research, Dr. Kim’s team identified CD63 as a cell surface­binding partner for TIMP­1, which is critical for human breast epithelial cell survival.

The study team acknowledges that future research aimed at unveiling the functions of TIMP-1 at the molecular level would greatly enhance the understanding of breast cancer progression. This information may also be useful in designing other interventions.

Citation: Jung KK, Liu XW, Chirco R, Fridman R, Kim HR. Identification of CD63 as a tissue inhibitor of metalloproteinase-1 interacting cell surface protein. EMBO J. 2006 Sep 6;25(17):3934-42.