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

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-1 beta-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.

Automated summary

This study reveals the role of pro-atherogenic environment and low-grade inflammation in tumor progression. Feeding mice with a high fat high cholesterol diet increases certain type of monocytes that are available for melanoma development. These cells, which accumulate in the tumor microenvironment, enhance pro-angiogenic and immunosuppressive activities. Limiting their accumulation or targeting specific protein production can slow down tumor growth. These findings shed light on the communication between cardiovascular diseases and cancer.