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

JAWORSKI, FELIPE; GUERON, GERALDINE; GENTILINI, LUCAS; LEONARDI, DAIANA; GONZALES PEREZ, IGNACIO; CONTRUFO, GERALDINE; RABINOVICH, GABRIEL A.; COMPAGNO, DANIEL G.; LADERACH, DIEGO; VAZQUEZ, ELBA

Philadelphia

Congreso; Annual Meeting ACCR; 2015

AACR

Prostate cancer (PCa) is the second leading cause of cancer death in men in the United States, and inflammation is recognized asa risk factor. In this regard we have previously shown that Heme Oxygenase-1 (HO-1) over-expression plays a critical role inprostate tumor cells per se by impairing cell proliferation, invasion and migration in vitro and tumor growth in vivo. In the presentstudy, we aimed to assess the role of stromal HO-1 in PCa. The stroma was conditioned by subcutaneously (s.c.) injectingC57BL/6 mice with 200µl of hemin (30µM; HO-1 pharmacological inducer) or its vehicle PBS on days 8, 5 and 1 prior to tumorchallenge. TRAMP-C1 cells (T-C1; 2x106 isogenic murine PCa cells) were s.c. injected on the same flank in Matrigel®. Hemin pretreatedanimals showed a significant increase in tumor latency (12-day delay when compared to control mice; Mantel-Cox test,P