Antagonistic Action of Hyaluronan Oligomers in Breast Cancer.
Abstract
The cell surface hyaluronan receptor, CD44H, has been shown to promote progression of B16F10 murine melanoma in vivo, but the involvement of hyaluronan-CD44 interactions in this process remains unclear. Recently, we demonstrated de novo synthesis of soluble, secreted isoforms of CD44 via alternative splicing of novel exonic sequences. Since soluble CD44 would be expected to antagonize interaction between hyaluronan and membrane bound CD44, we investigated whether stable transfection of malignant tumor cells with cDNA encoding soluble CD44 would prevent their ability to form tumors in vivo. In the present study, we have used a murine mammary carcinoma line (TA3/St) which grows in ascites form and metastasizes through the peritoneal wall of syngeneic mice; these cells express CD44 and attach to regions of the peritoneal wall enriched in hyaluronan prior to invasion through the wall. We now find that when transfected TA3/St cells overexpressing soluble CD44 are injected intraperitoncally, they fail to attach and form widespread tumors in the peritoneal wall whereas wild type TA3/St cells or transfectants carrying vector alone form tumors rapidly and consistently. Also, unlike mice injected with wild type or mock-transfected cells, the mice injected with soluble CD44 transfectants do not accumulate ascites, indicating that tumor cell growth therein is also markedly reduced. These results together with our previous work imply strongly that soluble CD44 acts in this system as an antagonist of interactions between hyaluronan and membrane-bound CD44H that are essential for TA3/St tumor progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1997
- Accession Number
- ADA336695
Entities
People
- Rebecca A. Peterson
Organizations
- Tufts University