Inhibition of Ovarian Cancer Chemoresistance and Metastasis with Antagonists of Hyaluronan-CD44-CD147 Interactions
Abstract
The overall objective of our work on human ovarian carcinoma cells is to apply our findings on the role of hyaluronan-CD44-CD147 interactions in drug resistance to improvement of therapy for malignant ovarian carcinoma. In previous work we showed that small hyaluronan oligosaccharides sensitize drug-resistant human ovarian carcinoma cells to various chemotherapeutic agents in culture and in vivo. In this grant period, we have: a) shown that drug-resistant Hey-A8-MDR human ovarian carcinoma cells contain CD133-positive/ CD147-positive/ CD44-positive cancer stem-like cells, as are also found in human patient ascites-derived ovarian carcinoma cells, thus documenting their suitability for our studies; b) completed preparation of hyaluronan oligosaccharide conjugated to the chemotherapeutic agent, docetaxel; we anticipate that this conjugate will show increased efficacy in vivo; c) identified a highly active siRNA against the regulator of hyaluronan synthesis, CD147, that sensitizes Hey-A8-MDR ovarian carcinoma cells to docetaxel and is currently being used to load nanoparticles for higher efficacy in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2014
- Accession Number
- ADA611022
Entities
People
- Bryan P. Toole
Organizations
- Medical University of South Carolina