CD29 and CD7 mediate galectin-3-induced type II T-cell apoptosis

• Published in: Cancer research (Chicago, Ill.) Ill.), 2003-12, Vol.63 (23), p.8302-8311
• Main Authors: FUKUMORI, Tomoharu, TAKENAKA, Yukinori, YOSHII, Tadashi, CHOI KIM, Hyeong-Reh, HOGAN, Victor, INOHARA, Hidenori, KAGAWA, Susumu, RAZ, Avraham
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD7 - metabolism; Antigens, CD7 - physiology; Antineoplastic agents; Apoptosis - drug effects; Apoptosis - immunology; Biological and medical sciences; Caspase Inhibitors; Caspases - metabolism; Enzyme Activation; Galectin 3 - genetics; Galectin 3 - metabolism; Galectin 3 - pharmacology; Humans; Integrin beta1 - metabolism; Integrin beta1 - physiology; Jurkat Cells; Lymphocyte Activation; Medical sciences; Mice; Mice, Inbred BALB C; Pharmacology. Drug treatments; T-Lymphocytes - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Transfection; Tumors
• ISSN: 0008-5472; 1538-7445

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.