Role of CD44 in Tumor Progression
Final rept. 1 Sep 1994-31 Aug 1999
GEORGETOWN UNIV WASHINGTON DC
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This project is concerned with the role of hyaluronan HA in tumor progression. Initially, we postulated that CD44 and HA played a role in angiogenesis. However, our studies suggested that this hypothesis was probably not correct. Subsequently, we attempted to target tumor-associated HA with an HA-binding complex HAbc that we isolated from cartilage by affinity chromatography. We found that the HAbc was able to block the growth of tumors cells in mice as well as in the chorioallantoic membrane CAM of chicken embryos. Furthermore, when HAbc was added to the medium of cultured endothelial cells, growth of these cells was inhibited in a dose-dependent fashion. Staining of these endothelial cells with Hoechst dye and analysis by flow cytometry suggested that this effect was due to the induction of apoptosis. In addition, when HAbc was injected i.v. into 10 day chicken embryos, it inhibited VEGF-induced angiogenesis in the CAM, indicative of anti-angiogenic activity. In each case, the effect was blocked by either heat- inactivation of the preparation or by premixing it with HA. Collectively, these results suggest that the binding of HAbc to HA of endothelial cells and induces apoptosis in these cells that, in turn, inhibits tumor vascularization and growth.
- Anatomy and Physiology
- Medicine and Medical Research