Induction of apoptosis of metastatic mammary carcinoma cells in vivo by disruption of tumor cell surface CD44 function.

Détails

ID Serval
serval:BIB_C68A3052F771
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Induction of apoptosis of metastatic mammary carcinoma cells in vivo by disruption of tumor cell surface CD44 function.
Périodique
Journal of Experimental Medicine
Auteur(s)
Yu Q., Toole B.P., Stamenkovic I.
ISSN
0022-1007[print], 0022-1007[linking]
Statut éditorial
Publié
Date de publication
1997
Volume
186
Numéro
12
Pages
1985-1996
Langue
anglais
Résumé
To understand how the hyaluronan receptor CD44 regulates tumor metastasis, the murine mammary carcinoma TA3/St, which constitutively expresses cell surface CD44, was transfected with cDNAs encoding soluble isoforms of CD44 and the transfectants (TA3sCD44) were compared 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 hyaluronan-producing cell monolayers. Mice intravenously injected with parental TA3/St cells developed 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 revealed that both cell types initially adhered to pulmonary endothelium and penetrated the interstitial 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 hyaluronan, they elicited abundant local hyaluronan production within invaded lung tissue, comparable to that induced by parental cells. These observations provide direct evidence that cell surface CD44 function promotes tumor cell survival in invaded tissue and that its suppression can induce apoptosis of the invading tumor cells, possibly as a result of impairing their ability to penetrate the host tissue hyaluronan barrier.
Mots-clé
Animals, Antigens, CD44/genetics, Antigens, CD44/physiology, Apoptosis, Female, Hyaluronic Acid/metabolism, Lung Neoplasms/secondary, Mammary Neoplasms, Experimental/immunology, Mammary Neoplasms, Experimental/metabolism, Mice, Mice, Inbred A, Mice, Nude, Neoplasm Invasiveness, Neoplasm Metastasis/immunology, Neoplasm Metastasis/pathology, Solubility, Stromal Cells/metabolism, Surface Properties, Transfection, Tumor Cells, Cultured, Tumor Escape
Pubmed
Création de la notice
26/08/2010 17:43
Dernière modification de la notice
03/03/2018 21:17
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