Differences in glycosylation patterns of heat shock protein, gp96: implications for prostate cancer prevention.
Heat shock protein gp96 induces a tumor-specific protective immunity in a variety of experimental tumor models. Because the primary sequences of the glycoprotein, gp96 are identical between tumor and normal tissues, the peptides associated with gp96 and/or the posttranslational modifications of gp96, determine its immunogenicity. Gp96-associated peptides constitute the antigenic repertoire of the source tissue; thus, purified gp96-peptide complexes have clinical significance as autologous cancer vaccines. However, the role of altered glycosylation and its contribution in the biological as well as immunologic activity of gp96 still remains uncharacterized. We examined the cancer-specific glycosylation patterns of gp96. To this end, monosaccharide compositions of gp96 were compared between normal rat prostate and two cancerous rat prostate tissues, nonmetastatic/androgen-dependent Dunning G and metastatic/androgen-independent MAT-LyLu, as well as two human nonmetastatic prostate cancer cell lines, androgen-dependent LnCaP and androgen-independent DU145. Marked differences were observed between the gp96 monosaccharide compositions of the normal and cancerous tissues. Furthermore, gp96 molecules from more aggressive cellular transformations were found to carry decreasing quantities of several monosaccharides as well as sum total content of neutral and amino sugars. We believe that the unique glycosylation patterns contribute to cellular phenotype and that the posttranslational modifications of gp96 may affect its functional attributes.
Suriano
Robert
R
Department of Microbiology and Immunology, New York Medical College, Valhalla, New York 10595, USA.
Ghosh
Salil K
SK
Ashok
Badithe T
BT
Mittelman
Abraham
A
Chen
Yuangen
Y
Banerjee
Asesh
A
Tiwari
Raj K
RK
D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D006031:Glycosylation; D006801:Humans; D008297:Male; D009005:Monosaccharides / Q000032:analysis; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000517:prevention & control; D051381:Rats
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D009005:Monosaccharides; C052646:sarcoma glycoprotein gp96 rejection antigens