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Introduction: The aim of this study was to determine if modification of the endothelin axis would alter the growth of murine prostate cancer as well as murine skin graft survivability.
Materials & Methods: One group of mice were injected with RM1 (prostate cancer) cells subcutaneously. Modified dendritic cells (DC) were injected into the contralateral flank. We used TNFa, BQ788 (ET_B receptor antagonist) and RM1 cell lysates for DC modification. In transplant experiments, Balb/C mice received an allographic skin transplant from C57B/6 mice and were treated either with BQ123(ET_A receptor antagonist) or water. Grafts were considered dead when complete separation was noted.
Results: In the prostate cancer experiment the mice were treated with DC alone (1), DC+TNFa(2), DC+RM1 lysate (3), DC+TNF+ BQ788 (4), and TNFa+BQ788+RM1 lysate (5). By day 28, mean tumor size reached 1824.08+229.86 mm³ in the Group 1, 1845.42+302.34 mm³ in the Group 2, 1502.67+367.13 mm³ in the Group 3, 1400.16+188.88 mm³ in Group 4, and 922.58+90.86 mm³ in Group 5. Difference in tumor sizes between Groups 1 and 5 was statistically significant (P=0.002). In the transplant experiment graft survival was 11.0+0.7 days in control group and 15.8+1.1 days in the group treated with BQ123 (P<0.001).

Conclusions: We have shown for the first time that modification of the endothelin axis on dendritic cells might alter immune response and prolong graft survival. Further, ET_B receptor blockade seems to stimulate proinflammatory immune response, a feature that may be useful in the treatment of malignant tumors.