Expression of chemokine-like receptor 1 (CMKLR1) on J744A.1 macrophages co-cultured with fibroblast and/or tumor cells: Modeling the influence of microenvironment

Maturation of macrophages is influenced by the composition of surrounding microenvironment. Expression of CMKLR1, the receptor for chemerin, is potentially associated with the differentiation status of macrophages. In this study, CMKLR1 was determined on peritoneal and tumor-infiltrating macrophages. CMKLR1 expression was found to be associated with the fibroblast-assisted maturation of J744A.1 monocyte/macrophage cells in the co-cultures established to model tumor microenvironment, whereas the presence of tumor cells was able to upregulate CMKLR1 expression independent of macrophage maturation. In addition, macrophages cultured with tumor cells or in tumor cell-conditioned media responded to recombinant chemerin(17-156) peptide and increased the expression of proinflammatory IL-1β, TNF-α and IL-12 p40 cytokines. The native form of chemerin (prochemerin) supplied by fibroblasts did not induce a functional response. These observations may indicate a potential role for chemerin and CMKLR1 in the regulation of inflammatory responses in the tumor microenvironment.

► CMKLR1 expression was found on tumor-infiltrating macrophages. ► The relationship between macrophages and fibroblasts and/or tumor cells was modeled. ► CMKLR1 expression was associated with the maturation of J744A.1 monocyte/macrophages. ► Tumor cells favor upregulation of CMKLR1 on macrophages independent of maturation. ► In macrophage-tumor co-cultures, chemerin enhanced proinflammatory gene expression.