Department of Basic Medicine, School of Medicine, Yangzhou University, Yangzhou, 225001, P. R. China.
Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou, 225001, P. R. China.
BMC Cancer. 2023 Oct 30;23(1):1042. doi: 10.1186/s12885-023-11519-5.
Adropin is encoded by the energy homeostasis-associated (ENHO) gene and widely present in liver, pancreas, heart, kidney, brain, and vascular tissues. Abnormal adropin is associated with metabolic, inflammatory, immune, and central nervous disorders. Whether adropin is involved in the development of colorectal cancer (CRC) is still unclear. Here, decreased adropin expression of tumor-nest cells in advanced-stage CRC was demonstrated. Adropin expressed by carcinoma cells was negatively correlated with macrophage infiltration in the matrix of CRC tissues. However, tumor macrophages enhanced adropin expression and were positively correlated with tumor invasion and metastasis. ENHO gene transfection into colon cancer (MC38) cells inhibited tumor growth in vivo, accompanying the increase of M1 macrophages. Treatment with low-dose adropin (< 100 ng/mL) on macrophages ex vivo directly increased mitochondrial reactive oxygen species for inflammasome activation. Furthermore, ENHO mice had less M1 macrophages in vivo, and ENHO macrophages were inert to be induced into the M1 subset ex vivo. Finally, low-dose adropin promoted glucose utilization, and high-dose adropin enhanced the expression of CPT1α in macrophages. Therefore, variations of adropin level in carcinoma cells or macrophages in tumor tissues are differently involved in CRC progression. Low-dose adropin stimulates the antitumor activity of macrophages, but high-dose adropin facilitates the pro-tumor activity of macrophages. Increasing or decreasing the adropin level can inhibit tumor progression at different CRC stages.
分泌素由能量平衡相关（ENHO）基因编码，广泛存在于肝脏、胰腺、心脏、肾脏、大脑和血管组织中。异常的分泌素与代谢、炎症、免疫和中枢神经系统紊乱有关。分泌素是否参与结直肠癌（CRC）的发生尚不清楚。本研究显示，在晚期 CRC 的肿瘤巢细胞中存在分泌素表达减少的现象。癌细胞表达的分泌素与 CRC 组织基质中巨噬细胞浸润呈负相关。然而，肿瘤巨噬细胞增强了分泌素的表达，并与肿瘤侵袭和转移呈正相关。ENHO 基因转染入结肠癌细胞（MC38）后，体内肿瘤生长受到抑制，同时伴随着 M1 巨噬细胞的增加。在体外对巨噬细胞进行低剂量（<100ng/ml）的分泌素处理可直接增加线粒体活性氧物质以激活炎症小体。此外，ENHO 小鼠体内的 M1 巨噬细胞较少，ENHO 巨噬细胞在体外不易被诱导为 M1 亚群。最后，低剂量的分泌素促进了巨噬细胞的葡萄糖利用，而高剂量的分泌素增强了巨噬细胞中 CPT1α 的表达。因此，肿瘤组织中癌细胞或巨噬细胞中分泌素水平的变化不同程度地参与了结直肠癌的进展。低剂量的分泌素刺激巨噬细胞的抗肿瘤活性，而高剂量的分泌素促进巨噬细胞的促肿瘤活性。增加或减少分泌素水平可以在不同的 CRC 阶段抑制肿瘤进展。
