From the

To understand how the hyaluronan receptor CD44 regulates tumor metastasis, the murine mam-mary carcinoma TA3/St, which constitutively expresses cell surface CD44, was transfected with cDNAs encoding soluble isoforms of CD44 and the transfectants (TA3sCD44) were com-pared with parental cells (transfected with expression vector only) for growth in vivo and in vitro. Local release of soluble CD44 by the transfectants inhibited the ability of endogenous cell surface CD44 to bind and internalize hyaluronan and to mediate TA3 cell invasion of hyaluro-nan-producing cell monolayers. Mice intravenously injected with parental TA3/St cells devel-oped massive pulmonary metastases within 21–28 d, whereas animals injected with TA3sCD44 cells developed few or no tumors. Tracing of labeled parental and transfectant tumor cells re-vealed that both cell types initially adhered to pulmonary endothelium and penetrated the in-terstitial stroma. However, although parental cells were dividing and forming clusters within lung tissue 48 h following injection, 80 % of TA3sCD44 cells underwent apoptosis. Although sCD44 transfectants displayed a marked reduction in their ability to internalize and degrade hy-aluronan, they elicited abundant local hyaluronan production within invaded lung tissue, com