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O-Glycosylation Regulates LNCaP Prostate Cancer Cell Susceptibility to Apoptosis Induced by Galectin-1

¹ Department of Pathology and ² Jonsson Comprehensive Cancer Center, School of Medicine, University of California at Los Angeles, Los Angeles, California; ³ Research Center for Molecular Endocrinology and WHO CCR, Biocenter Oulu, University of Oulu, Oulu, Finland; and ⁴ Department of Biological and Environmental Sciences, Division of Biochemistry, University of Helsinki, Helsinki, Finland

Requests for reprints: Linda G. Baum, Department of Pathology and Laboratory Medicine, School of Medicine, University of California at Los Angeles, 10833 LeConte Avenue, Los Angeles, CA 90095-1732. Phone: 310-206-5985; E-mail: lbaum{at}mednet.ucla.edu.

Resistance to apoptosis is a critical feature of neoplastic cells. Galectin-1 is an endogenous carbohydrate-binding protein that induces death of leukemia and lymphoma cells, breast cancer cells, and the LNCaP prostate cancer cell line, but not other prostate cancer cell lines. To understand the mechanism of galectin-1 sensitivity of LNCaP cells compared with other prostate cancer cells, we characterized glycan ligands that are important for conferring galectin-1 sensitivity in these cells, and analyzed expression of glycosyltransferase genes in galectin-1–sensitive, prostate-specific antigen–positive (PSA⁺) LNCaP cells compared with a galectin-1–resistant PSA^– LNCaP subclone. We identified one glycosyltransferase, core 2 N-acetylglucosaminyltransferase, which is down-regulated in galectin-1–resistant PSA^– LNCaP cells compared with galectin-1–sensitive PSA⁺ LNCaP cells. Intriguingly, this is the same glycosyltransferase required for galectin-1 susceptibility of T lymphoma cells, indicating that similar O-glycan ligands on different polypeptide backbones may be common death trigger receptors recognized by galectin-1 on different types of cancer cells. Blocking O-glycan elongation by expressing 2,3-sialyltransferase 1 rendered LNCaP cells resistant to galectin-1, showing that specific O-glycans are critical for galectin-1 susceptibility. Loss of galectin-1 susceptibility and synthesis of endogenous galectin-1 has been proposed to promote tumor evasion of immune attack; we found that galectin-1–expressing prostate cancer cells killed bound T cells, whereas LNCaP cells that do not express galectin-1 did not kill T cells. Resistance to galectin-1–induced apoptosis may directly contribute to the survival of prostate cancer cells as well as promote immune evasion by the tumor. [Cancer Res 2007;67(13):6155–62]

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