Antagonistic Action of Hyaluronan Oligomers in Breast Cancer
Abstract
The objective of this project was to determine whether hyaluronan interactions are involved in growth and invasion of tumor cells, especially mammary carcinoma. Our working hypothesis is that polymeric hyaluronan interacts in a multivalent manner with cell surface receptors such as CD44, thus inducing clustering of these receptors and concomitant intracellular signaling that leads to altered cell behavior typical of tumor cells. To test this hypothesis, two means of perturbing hyaluronan-protein interactions in vitro and in vivo have been employed in our studies. First, cDNA transfection and recombinant adenovirus infection have been used to over- express soluble hyaluronan-binding proteins in tumor cells; these proteins would be expected to act as a sink that competes for binding of endogenous hyaluronan. Second, tumor cells have been treated with hyaluronan oligomers; the oligomers compete for multivalent binding of endogenous polymeric hyaluronan by binding to receptors monovalently. Our results have shown that such perturbations of hyaluronan interactions inhibit tumor cell growth in vivo, anchorage-independent growth in soft agar, and invasion through extracellular matrix in vitro. The results of these studies provide strong evidence for the direct involvement of hyaluronan-tumor cell interactions in regulation of tumor growth and invasion.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2000
- Accession Number
- ADB267943
Entities
People
- Bryan P. Toole
- Jeanine Ward
- Rebecca L Peterson
Organizations
- Tufts University