Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China; Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Beijing, China; Cancer Institute of Capital Medical University, Beijing, China.
Exp Cell Res. 2021 Nov 15;408(2):112862. doi: 10.1016/j.yexcr.2021.112862. Epub 2021 Oct 6.
Macrophage receptor with collagenous structure (MARCO) is a member of the class A scavenger receptor family which is expressed on the cell surface of macrophages. It is well known that MARCO avidly binds to unopsonized pathogens, leading to its ingestion by macrophages. However, the role of MARCO in the recognition and phagocytosis of tumor cells by macrophages remains poorly understood. In this study, we used lentiviral technology to knockdown and overexpress MARCO and investigated the ability of macrophages to phagocytose tumor cells. Our results showed that MARCO expression was correlated with the ability of macrophages to carry on phagocytosis. MARCO knockdown led to significant decreases in the number of engulfment pseudopodia of macrophages and inhibition of the phagocytosis of tumor cells. On the other hand, MARCO overexpression elevated activity of SYK, PI3K and Rac1 in macrophages, which led to changes in macrophage morphology and enhanced phagocytosis by promoting formation of stress fibers and pseudopodia. By Co-IP analysis we showed that MARCO directly binds to the β5 integrin of SL4 tumor cells. In summary, these results demonstrated the important role for MARCO in demonstrated tumor cells uptake and clearance by macrophages.
MARCO 是巨噬细胞表面表达的 A 类清道夫受体家族的成员，它具有胶原结构的巨噬细胞受体。众所周知，MARCO 可以与未被调理的病原体结合，从而被巨噬细胞吞噬。然而，MARCO 在巨噬细胞识别和吞噬肿瘤细胞中的作用仍知之甚少。在这项研究中，我们使用慢病毒技术敲低和过表达 MARCO，并研究巨噬细胞吞噬肿瘤细胞的能力。我们的结果表明，MARCO 的表达与巨噬细胞吞噬能力相关。MARCO 敲低导致巨噬细胞吞噬伪足的数量显著减少，并且抑制了肿瘤细胞的吞噬作用。另一方面，MARCO 的过表达增加了巨噬细胞中 SYK、PI3K 和 Rac1 的活性，这导致了巨噬细胞形态的变化，并通过促进应力纤维和伪足的形成来增强吞噬作用。通过 Co-IP 分析，我们表明 MARCO 直接与 SL4 肿瘤细胞的β5 整合素结合。总之，这些结果表明 MARCO 在巨噬细胞摄取和清除肿瘤细胞中起着重要作用。
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