Role of Proteases in Breast Cancer Progression.
Annual rept. 1 Jul 95-30 Jun 96,
WAYNE STATE UNIV DETROIT MI
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Metastasis is the major cause of death in breast cancer patients. Metastasis formation depends on the ability of the tumor cells to degrade extracellular matrices ECM using specialized proteinases including the matrix metallo-proteinases MMPs and cathepsins. We have studied the regulation of activation and plasma membrane localization of MMP-2 and MMP-9, two members of the MMP family, and cathepsin B in breast epithelial and fibroblast cells. For these studies it was necessary to isolate primary breast fibroblasts. In this report we show the isolation and characterization of primary breast fibroblasts derived from normal and tumor tissue and the expression of MMPs and cathepsin B. Studies were carried out to establish the role of tumor-stroma interactions and the extracellular matrix on the expression of MMPs, TIMPs and cathepsin B. We also report on the nature of the association of MMP-9 to the surface of breast epithelial cells. Experiments in progress will study the role of stromal fibroblasts on proteases MMPs, cathepsin B in cell surface localization and activation in breast cancer cells.
- Anatomy and Physiology
- Medicine and Medical Research