Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6Chi monocytes and differentiation to pro-angiogenic myeloid cells

Thi Tran, Jean-Remi Lavillegrand, Cedric Lereverend, Bruno Esposito, Lucille Cartier, Melanie Montabord, Jaouen Tran-Rajau, Marc Diedisheim, Nadège Gruel, Khadija Ouguerram, Lea Paolini, Olivia Lenoir, Emmanuel Pinteaux, Eva Brabencova, Corinne Tanchot, Pauline Urquia, Jacqueline Lehmann-Che, Richard Le Naour, Yacine Merrouche, Christian Stockmann, Ziad Mallat, Alain Tedgui, Hafid Ait-Oufella, Eric Tartour and Stephane Potteaux ()
Additional contact information
Thi Tran: Université Paris Cité, Inserm, PARCC
Jean-Remi Lavillegrand: Université Paris Cité, Inserm, PARCC
Cedric Lereverend: Université de Reims Champagne Ardenne, IRMAIC EA 7509
Bruno Esposito: Université Paris Cité, Inserm, PARCC
Lucille Cartier: Université de Reims Champagne Ardenne, IRMAIC EA 7509
Melanie Montabord: Université Paris Cité, Inserm, PARCC
Jaouen Tran-Rajau: Université Paris Cité, Inserm, PARCC
Marc Diedisheim: Service de diabétologie, Hôpital Cochin APHP. GlandOmics, Cheverny
Nadège Gruel: INSERM U830, Équipe Labellisée LNCC, Diversity and Plasticity of Childhood Tumors Lab, PSL Research University, Institut Curie Research Centre, Institut Curie
Khadija Ouguerram: Université de Nantes, INRAE, UMR 1280 PhAN
Lea Paolini: Université Paris Cité, Inserm, PARCC
Olivia Lenoir: Université Paris Cité, Inserm, PARCC
Emmanuel Pinteaux: University of Manchester
Eva Brabencova: Institut Godinot
Corinne Tanchot: Université Paris Cité, Inserm, PARCC
Pauline Urquia: Université Paris Cité, Inserm, PARCC
Jacqueline Lehmann-Che: U976 HIPI
Richard Le Naour: Université de Reims Champagne Ardenne, IRMAIC EA 7509
Yacine Merrouche: Université de Reims Champagne Ardenne, IRMAIC EA 7509
Christian Stockmann: Université Paris Cité, Inserm, PARCC
Ziad Mallat: Université Paris Cité, Inserm, PARCC
Alain Tedgui: Université Paris Cité, Inserm, PARCC
Hafid Ait-Oufella: Université Paris Cité, Inserm, PARCC
Eric Tartour: Université Paris Cité, Inserm, PARCC
Stephane Potteaux: Université Paris Cité, Inserm, PARCC

Nature Communications, 2022, vol. 13, issue 1, 1-15

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 Ly6Chi 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.

Date: 2022
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DOI: 10.1038/s41467-022-33034-0

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