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) : Baum, Linda G.


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA413351


Report Date : DEC 2002


Pagination or Media Count : 21


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.


Descriptors :   *EPITHELIUM , *PROSTATE GLAND , *PROSTATE CANCER , NEOPLASMS , THERAPY , T LYMPHOCYTES , CELLS(BIOLOGY) , RESISTANCE(BIOLOGY) , GLYCOSIDES , ANDROGENS , LYMPHATIC SYSTEM , APOPTOSIS.


Subject Categories : ANATOMY AND PHYSIOLOGY
      MEDICINE AND MEDICAL RESEARCH


Distribution Statement : APPROVED FOR PUBLIC RELEASE