CD29 and CD7 mediate galectin-3-induced type II T-cell apoptosis.
Galectin (Gal)-3, a M(r) 31000 member of the beta-galactoside-binding protein family, is a multifunctional protein implicated in a variety of biological functions, including tumor cell adhesion, proliferation, differentiation, angiogenesis, apoptosis, cancer progression, and metastasis. Here, we report that secreted extracellular Gal-3 can signal apoptosis of human T leukemia cell lines, human peripheral blood mononuclear cells, and activated mouse T cells after binding to cell surface glycoconjugate receptors through carbohydrate-dependent interactions because the apoptotic effect was found to be inhibited by lactose, specific sugar inhibitor, and to be dose dependent. However, the apoptosis sensitivity to Gal-3 varied among the different cell lines tested. We report that Gal-3-null Jurkat, CEM, and MOLT-4 cells were significantly more sensitive to exogenous Gal-3 than SKW6.4 and H9 cells, which express Gal-3, suggesting a cross-talk between the antiapoptotic activity of intracellular Gal-3 and proapoptotic activity of extracellular Gal-3. Furthermore, Gal-3-transfected CEM cells were found to be more resistant to C(2)-ceramide-induced apoptosis than the control CEM cells. Identification of Gal-3 cell surface receptors revealed that Gal-3 binding to CD7 and CD29 (beta(1) integrin) induced apoptosis. Gal-3 binding to its cell surface receptors results in activation of mitochondrial apoptosis events including cytochrome c release and caspase-3 activation, but not caspase-8 activation. Taken together, these results suggest that the induction of T-cell apoptosis by secreted Gal-3 may play a role in the immune escape mechanism during tumor progression through the induction of apoptosis to cancer-infiltrating T cells. The induction of T-cell apoptosis by secreted Gal-3 is dependent in part on the presence or absence of cytoplasmic Gal-3, providing a new insight for the immune escape mechanism of cancer cells.
Fukumori
Tomoharu
T
Tumor Progression and Metastasis Program, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, USA.
Takenaka
Yukinori
Y
Yoshii
Tadashi
T
Kim
Hyeong-Reh Choi
HR
Hogan
Victor
V
Inohara
Hidenori
H
Kagawa
Susumu
S
Raz
Avraham
A
D000818:Animals; D019011:Antigens, CD7 / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism / Q000502:physiology*; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014162:Transfection
D019011:Antigens, CD7; D061945:Caspase Inhibitors; D037502:Galectin 3; D019012:Integrin beta1; D020169:Caspases