Published online Sep 14, 2022. doi: 10.3748/wjg.v28.i34.4993
Peer-review started: March 14, 2022
First decision: April 11, 2022
Revised: May 15, 2022
Accepted: August 22, 2022
Article in press: August 22, 2022
Published online: September 14, 2022
Oxidized 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.
To investigate the role of ox-LDL through macrophages in HFD associated CRC.
The 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 poly
The 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.
Ox-LDL stimulates CD206+ macrophages to upregulate CD44 and CD133 expression in HFD related CRC.
Core Tip: Obesity increases the risk of colorectal cancer (CRC), but the mechanism remains unknown. CD206+ macrophages promote CRC. It has been established that the prevalence of CRC was higher in people consuming a high-fat diet (HFD) and HFD fed mice with up-regulated CD206+ macrophages levels in colorectal tissue. Oxidized low-density lipoprotein (ox-LDL) is a lipid peroxide which has been found to be increased in serum of CRC patients. Importantly, ox-LDL exerts a regulatory effect on macrophages and may regulate CRC through the tumor microenvironment. Our study showed that ox-LDL stimulates CD206+ macrophages to up-regulate CD44 and CD133 expression in HFD associated CRC.