Tumor prevention and antitumor immunity with heat shock protein 70 induced by 15-deoxy-delta12,14-prostaglandin J2 in transgenic adenocarcinoma of mouse prostate cells.
The biological modifier delta12-prostaglandin J2 and related prostaglandins have been reported to have significant growth-inhibitory activity with induction of heat shock proteins (Hsps). Tumor-derived Hsps have been shown previously to elicit specific immunity to tumors from which they are isolated. In this study, 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2)-induced Hsp70 was purified from transgenic adenocarcinoma mouse prostate cells (TRAMP-C2). It was then tested for its ability to activate specific CTLs and induce protective immunity against prostate cancer in C57BL/6 mice. Treatment of cells with 8.0 microM 15d-PGJ2 for 24 h caused significant induction of Hsp70 expression. The yield of Hsp70 purified from 15d-PGJ2-treated cells was 4-5-fold higher when compared with untreated TRAMP-C2 cells. Vaccination of mice with Hsps isolated from TRAMP-C2 cells elicited tumor-specific CTLs and prevented the growth of TRAMP-C2 tumors. These results indicate that the induced heat shock proteins may have promising applications for antitumor, T-cell immunotherapy. In particular, these findings have important implications for the development of novel anticancer therapies aimed at promoting an immune response to prostate tumors.
Vanaja
D K
DK
Department of Urology, Mayo Clinic/Foundation, Rochester, Minnesota 55905, USA.
Grossmann
M E
ME
Celis
E
E
Young
C Y
CY
D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000276:immunology* / Q000302:isolation & purification; D007113:Immunity, Innate / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000517:prevention & control; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; D007155:Immunologic Factors; D015230:Prostaglandin D2