Oxidized low-density lipoprotein stimulates CD206 positive macrophages upregulating CD44 and CD133 expression in colorectal cancer with high-fat diet

• Published in: World journal of gastroenterology : WJG Vol. 28; no. 34; pp. 4993 - 5006
• Main Authors: Zheng, Shi-Min, Chen, Hao, Sha, Wei-Hong, Chen, Xiao-Fen, Yin, Jian-Bin, Zhu, Xiao-Bo, Zheng, Zhong-Wen, Ma, Juan
• Format: Journal Article
• Language: English
• Published: Baishideng Publishing Group Inc 14.09.2022
• Subjects: Basic Study
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v28.i34.4993

BACKGROUNDOxidized low-density lipoprotein (ox-LDL), which is abnormally increased in the serum of colorectal cancer (CRC) patients consuming a high-fat diet (HFD), may be one of the risk factors for the development of CRC. Ox-LDL exerts a regulatory effect on macrophages and may influence CRC through the tumor microenvironment. The role of ox-LDL in CRC remains unclear. AIMTo investigate the role of ox-LDL through macrophages in HFD associated CRC. METHODSThe expression of ox-LDL and CD206 was detected in colorectal tissues of CRC patients with hyperlipidemia and HFD-fed mice by immunofluorescence. We stimulated the macrophages with 20 μg/mL ox-LDL and assessed the expression levels of CD206 and the cytokines by cell fluorescence and quantitative polymerase chain reaction. We further knocked down LOX-1, the surface receptor of ox-LDL, to confirm the function of ox-LDL in macrophages. Then, LoVo cells were co-cultured with the stimulated macrophages to analyze the CD44 and CD133 expression by western blot. RESULTSThe expression of ox-LDL and the CD206 was significantly increased in the stroma of colorectal tissues of CRC patients with hyperlipidemia, and also upregulated in the HFD-fed mice. Moreover, an increased level of CD206 and decreased level of inducible nitric oxide synthase were observed in macrophages after ox-LDL continuous stimulation. Such effects were inhibited when the surface receptor LOX-1 was knocked down in macrophages. Ox-LDL could induce CD206+ macrophages, which resulted in high expression of CD44 and CD133 in co-cultured LoVo cells. CONCLUSIONOx-LDL stimulates CD206+ macrophages to upregulate CD44 and CD133 expression in HFD related CRC.