Antagonistic Action of Hyaluronan Oligomers in Breast Cancer.
Abstract
The murine mammary carcinoma, TA3/St, grows aggressively in ascites and rapidly invades the peritoneal wall of syngeneic mice. The hyaluronan content of ascites increases markedly during TA3/St cell proliferation therein and hyaluronan is enriched at sites of attachment of these cells to the peritoneal wall. Thus we have investigated whether interference with interaction between hyaluronan and CD44 on the TA3/st cell surface, by overexpression of soluble-CD 44, would inhibit ascites tumor progression. Mice injected intraperitoneally with stable transfectants of TA3/St cells that overexpress soluble CD44 did not accumulate ascites fluid; the transfectants grew at a reduced rate within the peritoneum, then went into G1 arrest. However, transfectants overexpressing mutant soluble CD44 that does not bind hyaluronan exhibited similar ascites accumulation, growth rates and cell cycle profiles in vivo to wild type and vector transfected TA3/St cells. The soluble CD44-transfected TA3/St cells also failed to attach and form tumors in the peritoneal wall. In contrast, wild type TA3/St cells, and transfectants carrying vector alone or mutant soluble-CD44, formed such tumors rapidly and consistently. Thus, soluble CD44 acts as an antagonist of hyaluronan interactions that are essential for TA3/St tumor progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADA377165
Entities
People
- Rebecca A. Peterson
Organizations
- Tufts University