Inflammatory Molecule, PSGL-1, Deficiency Activates Macrophages to Promote Colorectal Cancer Growth through NFκB Signaling (Publication with Expression of Concern. See vol. 18, pg. 939, 2020) (Retracted Article)
Inflammatory Molecule, PSGL-1, Deficiency Activates Macrophages to Promote Colorectal Cancer Growth through NFκB Signaling (Publication with Expression of Concern. See vol. 18, pg. 939, 2020) (Retracted Article)
复制标题
炎症分子 PSGL-1 缺乏会激活巨噬细胞，通过 NF kappa B 信号传导促进结直肠癌生长
DOI：
10.1158/1541-7786.mcr-16-0309
复制
发表时间：
2017-04-01
影响因子：
5.2
通讯作者：
Wang, Lijing
中科院分区：
文献类型：
--
作者：
Li, Jiangchao;Zhou, Zeqi;Wang, Lijing
p -选择素糖蛋白配体1 （SELPLG/PSGL-1）是一种炎症分子，在功能上与免疫细胞分化和白细胞动员有关。然而，PSGL-1在肿瘤发展中的作用尚不清楚。因此，本研究探讨PSGL-1在结直肠癌肠道肿瘤发生发展中的机制作用。Apc（Min/+）小鼠极易自发肠腺瘤形成，并与psgl1缺失小鼠杂交，获得Apc（Min/+）复合转基因小鼠；PSGL-1(- /)基因型。比较Apc（Min/+）小鼠与Apc（Min/+）小鼠肠道肿瘤的发生率及病理特征；PSGL-1(- /)小鼠。重要的是，psgl -1缺陷小鼠对肠道肿瘤的易感性增加，肿瘤生长加速。在机制上，psgl -1缺陷小鼠中发现小鼠趋化因子配体9 （CCL9/MIP-1 γ）的产生增加，巨噬细胞可能是巨噬细胞炎症蛋白-1 γ (MIP-1 γ)的主要来源。体外研究表明，巨噬细胞源性MIP-1g通过激活NF κ B信号通路促进结直肠癌肿瘤细胞生长。相反，通过骨髓移植恢复PSGL-1信号可以减少MIP-1g的产生并减弱Apc的能力（Min/+）；PSGL-1(-/)-小鼠产生肠道肿瘤。在人类结直肠癌临床标本中，psgl -1阳性细胞的存在与有利的肿瘤转移分期和减少淋巴结转移有关。意义：PSGL-1缺乏和炎症通过MIP-1g/NF κ B信号轴使肠组织更容易发生结直肠肿瘤。(c) 2017 aacr。
P-selectin glycoprotein ligand 1 (SELPLG/PSGL-1) is an inflammatory molecule that is functionally related to immune cell differentiation and leukocyte mobilization. However, the role of PSGL-1 in tumor development remains unknown. Therefore, this study investigates the mechanistic role of PSGL-1 in the development of intestinal tumors in colorectal cancer. Apc(Min/+) mice are highly susceptible to spontaneous intestinal adenoma formation, and were crossbred with PSGL1-null mice to generate compound transgenic mice with a Apc(Min/+); PSGL-1(-/)-genotype. The incidence and pathologic features of the intestinal tumors were compared between the Apc(Min/+) mice and Apc(Min/+); PSGL-1(-/)-mice. Importantly, PSGL-1-deficient mice showed increased susceptibility to develop intestinal tumors and accelerated tumor growth. Mechanistically, increased production of the mouse chemokine ligand 9 (CCL9/MIP-1 gamma) was found in the PSGL-1-deficient mice, and the macrophages are likely the major source of macrophage inflammatory protein-1 gamma (MIP-1 gamma). Studies in vitro demonstrated that macrophage-derived MIP-1g promoted colorectal cancer tumor cell growth through activating NF kappa B signaling. Conversely, restoration of the PSGL-1 signaling via bone marrow transplantation reduced MIP-1g production and attenuated the ability of Apc(Min/+); PSGL-1(-/)-mice to generate intestinal tumors. In human colorectal cancer clinical specimens, the presence of PSGL-1-positive cells was associated with a favorable tumornode-metastasis staging and decreased lymph node metastasis.Implications: PSGL-1 deficiency and inflammation render intestinal tissue more vulnerable to develop colorectal tumors through a MIP-1g/NF kappa B signaling axis. (C) 2017 AACR.