International Immunology, Vol. 13, No. 10, 1309-1319,
October 2001
© 2001 Japanese Society for Immunology
CD44 stimulation down-regulates Fas expression and Fas-mediated apoptosis of lung cancer cells
Second Department of Surgery and
1 First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu 807-8555, Japan
Correspondence to: Y. Tanaka
Cytotoxic T lymphocytes (CTL) play a major role in the rejection of tumor cells, but tumor rejection does not always occur in vivo, indicating that defects in anti-tumor immune responses may be common. We here document a novel function for CD44—using lung cancer cells, we showed that stimulation of CD44 reduced Fas expression and Fas-mediated apoptosis: (i) lung cancer cells expressed high levels of CD44; (ii) engagement of CD44 on the cells by a specific antibody or fragmented hyaluronan reduced Fas expression; (iii) CD44 cross-linking reduced Fas-mediated apoptosis; (iv) stimulation of CD44 on lung cancer cells decreased IFN-
production by autologous CTL; and (v) CD44 stimulation prevented killing of lung cancer cells by autologous CTL. Based on these findings, we postulate a new concept—that interaction of CD44 on lung cancer cells with fragments of extracellular hyaluronan present in the surrounding extracellular matrix reduces Fas expression as well as Fas-mediated apoptosis of cancer cells. This leads to reduced susceptibility of the cells to CTL-mediated cytotoxicity through the Fas–Fas ligand pathway.
Keywords: apoptosis, CD44, cytotoxic T lymphocytes, Fas, lung cancer
Transmitting editor: T. Hamaoka
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