Membrane-Bound Hyaluronidase in Breast Cancer Progression
Final rept. 1 Sep 1998-31 Aug 2002
GEORGETOWN UNIV WASHINGTON DC
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Using highly purified sperm hyaluronidase and PH-20 cDNA transfection approaches, we have demonstrated that PH-2O HAase can release FGF2, stimulates the growth of both tumor cells in both anchorage -dependent and independent conditions. It can also stimulate the proliferation of endothelial cells and enhance the tumor angiogenesis. As the result of the dual effect, PH-20 HAase promotes the tumor growth in vivo. The results of in situ hybridization and immunohlstochemistry staining indicate that both mRNA and protein of PH-20 HAase are expressed in breast cancer cells. While there is little staining in normal breast tissues, there is a strong staining in breast cancer cells. The expressing rate increases from primary breast tumors without metastasis 48.2 to those with metastasis 70.8 to those lymph node metastasis 83.3, strongly suggesting that the PH-20 HAase is utilized by malignant breast cancer cells to promote their progression. The detection of the level of PH-20 HAase may serve as a poor prognosis index for human breast cancer. The reduction of the expression or the function of PH-20 HAase by genetic modification anti-sense, ribozymes or siRNA or small molecules may be an novel approach in anti-breast cancer.
- Anatomy and Physiology