Accession Number:

ADA413351

Title:

Elucidation of a Novel Cell Death Mechanism in Prostate Epithelial Cells

Descriptive Note:

Annual rept. 19 Nov 2001-18 Nov 2002

Corporate Author:

CALIFORNIA UNIV LOS ANGELES

Personal Author(s):

Report Date:

2002-12-01

Pagination or Media Count:

21.0

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, DU145 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 susceptible 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 O-linked glycans on glycoproteins in contrast, N-glycans are not required 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 O-glycans that are recognized by galectin-1. 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 may allow novel therapeutic approaches to manipulate tumor cell glycosylation to overcome tumor cell resistance to apoptosis.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE