Engineering the tumor microenvironment: Hemin conditioning in vivo impairs tumor growth and reprograms the immune- modulatory response in prostate cancer

JAWORSKI, FELIPE MARTÍN; GUERON, GERALDINE; GENTILINI, LUCAS; LEONARDI, DAIANA; GONZALEZ PÉREZ, IGNACIO; CONTRUFO, GERALDINE; RABINOVICH, GABRIEL ADRIÁN; COMPAGNO, DANIEL; LADERACH, DIEGO JOSÉ; VAZQUEZ, ELBA SUSANA

Philadelphia

Congreso; American Association of Cancer Research Annual Meeting; 2015

American Association of Cancer Research

Prostate cancer (PCa) is the second leading cause of cancer death in men in the United States, and inflammation is recognized as a risk factor. In this regard we have previously shown that Heme Oxygenase-1 (HO-1) over-expression plays a critical role in prostate tumor cells per se by impairing cell proliferation, invasion and migration in vitro and tumor growth in vivo. In the present study, we aimed to assess the role of stromal HO-1 in PCa. The stroma was conditioned by subcutaneously (s.c.) injecting C57BL/6 mice with 200μl of hemin (30μM; HO-1 pharmacological inducer) or its vehicle PBS on days 8, 5 and 1 prior to tumor challenge. TRAMP-C1 cells (T-C1; 2x106 isogenic murine PCa cells) were s.c. injected on the same flank in Matrigel®. Hemin pre- treated animals showed a significant increase in tumor latency (12-day delay when compared to control mice; Mantel-Cox test, P