In vivo hemin pre-conditioning targets the vascular and immunological compartments and restrains prostate tumor development

FELIPE M JAWORSKI, LUCAS D GENTILINI, GERALDINE GUERON, ROBERTO P MEISS, EMILIANO G ORTIZ, PAULA M BERGUER, ASIF AHMED, NORA NAVONE, GABRIEL A RABINOVICH, DANIEL COMPAGNO, DIEGO LADERACH * & ELBA S VAZQUEZ* (*) COMPARTEN ÚLTIMA AUTORÍA.

Mar del Plata

Conferencia; Reunión Anual Sociedad Argentina de Investigación Clínica 2016; 2016

Prostate cancer (PCa) is the second most common cancer in men worldwide. Although most current therapies against this disease are designed to target the tumor cells themselves, the surrounding microenvironment plays a leading role in enabling the growth and dissemination of the tumor. Therefore, novel cancer therapies should consider the crosstalk between epithelial and stromal compartments, which has been reported to promote tumor progression by remodeling the extracellular matrix to enhance invasion and angiogenesis, releasing soluble factors required for tumor growth, and disarming the antitumor immune surveillance. Chronic inflammation has been increasingly associated with a high cancer incidence, providing clear evidence that a deregulated microenvironment affects tumorigenesis. Several molecular pathways have been linked to cancer and inflammation. In particular, the enzyme Heme Oxygenase-1 (HO-1) is part of an endogenous defence system implicated in the cellular homeostatic response. The intrinsic effect of HO-1 on tumor cells in different cancer models has been extensively addressed. Data are available from a wide spectrum of physiopathological conditions that link HO-1 to modulation of angiogenesis and the immune function, two important hallmarks of cancer. Particularly in PCa, we have demonstrated that HO-1-over-expressing human xenografts show impaired growth and angiogenesis, and that this protein modifies the bone microenvironment modulating PCa bone metastasis. Furthermore, we recently defined a novel role for HO-1 in shaping the architecture of cell-cell interactions, favoring a less aggressive phenotype. Moreover, HO-1 inhibited relevant pathways implicated in prostate tumorigenesis. However, in spite of considerable evidence regarding the role of this enzyme in the epithelial tumor cell compartment, its role in the tumour microenvironment still remains elusive. In this study we assessed whether pre-conditioning with hemin, known to induce HO-1, could affect PCa development using a fully immunocompetent murine model.