Increased hyaluronan at sites of attachment to mesentery by CD44-positive mouse ovarian and breast tumor cells

Yeo, T.K.; Nagy, J.A.; Yeo, K.T.; Dvorak, H.F.; Toole, B.P.

American Journal of Pathology 148(6): 1733-1740


ISSN/ISBN: 0002-9440
PMID: 8669459
Accession: 008849741

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The mouse ovarian ascites tumor, MOT, and mammary ascites tumor, TA3/St, served as models to follow changes in hyaluronan levels during tumor growth, attachment, and invasion. Subsequent to introduction of tumor cells into the peritoneal cavity, hyaluronan accumulated intraperitoneally and at the initial sites of attachment of tumor cells and cell clumps to the mesenteric surface; the latter co-localized with sites of fibrin deposition as reported earlier. Subsequently, high levels of hyaluronan accumulated throughout the interior of the mesentery. Because neither tumor cell line synthesized substantial amounts of hyaluronan in culture, the large accumulations observed in the mesenteries and ascites fluid of tumor-bearing animals most likely resulted from increased synthesis and secretion by peritoneal-lining mesothelial cells and/or fibroblasts in response to stimulation by the tumor cells or their products. TA3/St tumor cells were universally positive for the hyaluronan receptor, CD44, whereas approximately 90% of MOT tumor cells were CD44-negative. However, the great majority of MOT or TA3/St cells that initially attached to the mesentery were strongly CD44 positive. We propose that hyaluronan-rich matrix is involved in tumor cell attachment to the mesentery possibly via interaction with tumor cell surface CD44.