Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6Chi monocytes and differentiation to pro-angiogenic myeloid cells
Thi Tran, Jean‐Rémi Lavillegrand, Cédric Lerévérend, Bruno Esposito, Lucille Cartier, Mélanie Montabord, Jaouen Tran-Rajau, Marc Diedisheim, Nadège Gruel, Khadija Ouguerram, Léa Paolini, Olivia Lenoir, Emmanuel Pinteaux, Eva Brabencová, Corinne Tanchot, Pauline Urquia, Jacqueline Lehmann‐Che, Richard Le Naour, Yacine Merrouche, Christian Stockmann, Ziad Mallat, Alain Tedgui, Hafid Ait‐Oufella, Éric Tartour, Stéphane Potteaux
Abstract
Abstract Cancer and cardiovascular disease (CVD) share common risk factors such as dyslipidemia, obesity and inflammation. However, the role of pro-atherogenic environment and its associated low-grade inflammation in tumor progression remains underexplored. Here we show that feeding C57BL/6J mice with a non-obesogenic high fat high cholesterol diet (HFHCD) for two weeks to induce mild dyslipidemia, increases the pool of circulating Ly6C hi monocytes available for initial melanoma development, in an IL-1β-dependent manner. Descendants of circulating myeloid cells, which accumulate in the tumor microenvironment of mice under HFHCD, heighten pro-angiogenic and immunosuppressive activities locally. Limiting myeloid cell accumulation or targeting VEGF-A production by myeloid cells decrease HFHCD-induced tumor growth acceleration. Reverting the HFHCD to a chow diet at the time of tumor implantation protects against tumor growth. Together, these data shed light on cross-disease communication between cardiovascular pathologies and cancer.