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The Role of EMMPRIN in Tumor Progression

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Final Addendum rept. 1 May-30 Nov 2002

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Crucial steps in tumor progression and the process of metastasis, e.g. tumor growth, invasion through extracellular matrices and angiogenesis, involve proteolytic modification of the pericellular matrix surrounding tumor cells. A major class of proteases involved in these processes is the matrix metalloproteinases MMPs, and inhibition of MMPs prevents progression and metastasis of several tumor types, including human breast carcinomas, in animal models. In vivo, tumor MMPs are often produced by stromal cells associated with tumors as well as the tumor cells. The tumor cell surface glycoprotein, EMMPRlN, stimulates MMP production by fibroblasts and endothelial cells, and may be an important regulator of MMP production during tumorigenesis in vivo. However no direct evidence for its role in tumor progression had been published prior to this study. The focus of this proposal has been to demonstrate directly whether or not EMMPRIN promotes breast cancer progression, whether a role for EMMPRIN in tumor progression may be to promote or induce angiogenesis, and whether approaches can be developed that may have future therapeutic potential. In this addendum we have shown that increased expression of EMMPRIN also induces MMP production and increased invasiveness in phenotypically normal human mammary epithelial cells. Thus this study has shown that EMMPRIN promotes tumor growth and invasion and that interference with the action of EMMPRIN may be an effective way to retard breast carcinoma progression in patients.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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