PPAR\(\alpha\) Deficiency in Inflammatory Cells Suppresses Tumor Growth

Abstract

Inflammation in the tumor bed can either promote or inhibit tumor growth. Peroxisome proliferator-activated receptor (PPAR)\(\alpha\) is a central transcriptional suppressor of inflammation, and may therefore modulate tumor growth. Here we show that PPAR\(\alpha\) deficiency in the host leads to overt inflammation that suppresses angiogenesis via excess production of the endogenous angiogenesis inhibitor thrombospondin-1 and prevents tumor growth. Bone marrow transplantation and granulocyte depletion show that PPAR\(\alpha\) expressing granulocytes are necessary for tumor growth. Neutralization of thrombospondin-1 restores tumor growth in PPAR\(\alpha\)-deficient mice. These findings suggest that the absence of PPAR\(\alpha\) activity renders inflammatory infiltrates tumor suppressive and, thus, may provide a target for inhibiting tumor growth by modulating stromal processes, such as angiogenesis.