Elucidation of a Novel Cell Death Mechanism in Prostate Epithelial Cells
Abstract
Tumor cell resistance to apoptosis is a major obstacle to effective therapy of prostate cancer. We have found that the androgen dependent prostate cancer cell line LNCaP is sensitive to apoptosis induced by galectin-1, an endogenous human lectin that is abundant in prostate stroma. In contrast, androgen independent LNCaP, DUl45, and PC3 cells are resistant to galectin-1 induced death and actually synthesize galectin-1 and export it to the cell surface. Galectin-1 binds to saccharide ligands on suscepibel LNCaP cells to trigger cell death. Susceptibility to galectin-1 appears to depend on the presence of a specific class of cell surface glycans, the 0-linked glycans on glycoproteins; in contrast, N-glycans are not recuired for galectin-1 induced LNcaP cell death. Resistance to galectin-1 induced death correlates with markedly decreased expression of a specific glycosyltransferase, the C2GnT, which creates saccharide ligands on 0-glycans that are recognized by galectin-l. The C2GnT enzyme also regulates susceptibility of T cells to galectin-1 induced death, indicating that a common glycosylation pathway may control cell death in epithelial and lymphoid cells. Identification of a mechanism that enhances galectin-1 prostate cancer cell death mal allow novel therapeutic approaches to manipulate tumor cell glycosylation to overcome tumor cell resistance to apoptosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2003
- Accession Number
- ADA421357
Entities
People
- Linda G. Baum
Organizations
- University of California, Los Angeles