M-CSF from Cancer Cells Induces Fatty Acid Synthase and PPARβ/δ Activation in Tumor Myeloid Cells, Leading to Tumor Progression

Abstract

Introduction: Tumor myeloid cells have a central role in tumor progression. However, the mechanism by which the myeloid cells sense the tumor microenvironment and activate their pro-tumoral function remains unclear. Methods: Lewis lung carcinoma tumor model with PPARβ/δ-deficient bone marrow transplantation and adoptive transfer of wild-type macrophages were used to study the role of myeloid PPARβ/δ in tumor progression. Results: PPARβ/δ is strongly expressed and activated in tumor myeloid cells. PPARβ/δ promotes tumor growth and angiogenesis by inducing pro-tumoral phenotype of myeloid cells. This pro-tumoral phenotype, represented as IL-10 expression, stimulates tumor cell invasion and angiogenesis apart from its well-known immune regulatory function. Conclusions: The activation of PPARβ/δ in myeloid cell is dependent on increased fatty acid synthase expression, which is augmented by cancer cell derived cytokine, M-CSF.