EMMPRIN (extracellular matrix metalloproteinase inducer) binds to annexin II

H Guo, M.D., Ph.D, BP Toole, Ph.D.

Department of Anatomy & Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts

EMMPRIN is a member of the immunoglobulin superfamily that is present on the surface of tumor cells and stimulates adjacent stromal cells to synthesize matrix metalloproteinases (MMPs). In order to better understand the function of EMMPRIN we have been seeking binding partners that are involved in its action. We have shown that interstitial collagenase (MMP-1) is bound to EMMPRIN on the surface of tumor cells where it may more efficiently degrade collagen in the pericellular matrix of tumor cells (Guo et al., Cancer Research 60: 888-891, 2000). Recently, we have demonstrated that EMMPRIN also interacts with annexin II, a calcium-dependent phospholipid-binding protein. Using affinity purification, we isolated EMMPRIN-binding proteins of ~67 and ~39 kD from fibroblast cell membranes. Amino acid sequences of tryptic peptides from each of these were identical to sequences within annexin II. Pretreatment of membrane extracts with anti-annexin II antibody inhibited binding to EMMPRIN. Antibody to EMMPRIN also inhibited binding of EMMPRIN to annexin II. Furthermore, we observed that EMMPRIN and annexin II co-localize on the surface of LX-1 human lung carcinoma cells, possibly in lipid rafts within the cell membrane. We are currently exploring whether annexin II is involved in the mechanism whereby EMMPRIN induces MMP synthesis.

KEY WORDS: Collagenase, invasion, tumor stromal interactions.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Metastasis.