Elucidation of a Novel Cell Death Mechanism in Prostate Epithelial Cells
Abstract
Tumor cell resistance to apoptosis and immune attack are obstacles to effective prostate cancer therapy. Androgen dependent LNCaP prostate cancer cells are sensitive to apoptosis induced by galectin-l, a human lectin that is abundant in prostate stroma. In contrast, androgen independent LNCaP, DU145 and PC-3 cells are resistant to galectin-l induced death and express galectin-l on the cell surface. Galectin-l binds to specific saccharide ligands on LNCaP cells to trigger cell death; susceptibility to galectin-1 requires 0-linked glycans on glycoproteins, while N-glycans are not required for galectin-l induced cell death. Galecti-l resistance in androgen independent LNCaP cells correlates with decreased expression of a specific glycosyltransferase, C2GnT, that creates 0-glycan ligands recognized by galectin-l. Blocking Oglycan elongation by expressing a competing glycosyltransferase, ST3Gal I, renders LNCaP cells resistant to galectin-l death. Galectin-1 resistant DU145 and PC-3 cells can kill adherent T cells via cell surface gal-1. Moreover, PC-3 cells secrete a factor that up-regulates gal-1 expression by endothelial cells, which then can kill adherent T cells. Thus, enhancing galectin-1 prostate cancer cell death may allow novel therapeutic approaches to manipulate tumor cell glycosylation to overcome tumor cell resistance to apoptosis and to prevent tumor evasion of the immune response.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2004
- Accession Number
- ADA432559
Entities
People
- Linda G. Baum
Organizations
- University of California, Los Angeles