A reciprocal feedback between colon cancer cells and Schwann cells promotes the proliferation and metastasis of colon cancer.
A reciprocal feedback between colon cancer cells and Schwann cells promotes the proliferation and metastasis of colon cancer.
复制标题
结肠癌细胞与施万细胞之间的相互反馈促进结肠癌的增殖和转移
DOI：
10.1186/s13046-022-02556-2
复制
发表时间：
2022-12-15
影响因子：
11.3
通讯作者：
Zhao, Gang
中科院分区：
文献类型：
--
作者：
Han, Shengbo;Wang, Decai;Huang, Yan;Zeng, Zhu;Xu, Peng;Xiong, Hewei;Ke, Zunxiang;Zhang, Ya;Hu, Yuhang;Wang, Fan;Wang, Jie;Zhao, Yong;Zhuo, Wenfeng;Zhao, Gang
研究表明，结肠癌癌前病变周围雪旺细胞的出现可能是促进肿瘤发生的早期指标。本研究探讨了结肠癌细胞与雪旺细胞之间的通讯。免疫荧光分析检测雪旺细胞在结肠癌组织和正常结肠组织中的差异分布。采用CCK8实验、集落形成实验、伤口愈合实验和Transwell实验研究结肠癌细胞与雪旺细胞的相互作用。为进一步探讨结肠癌细胞对雪旺细胞的作用，分离了结肠癌细胞来源的外切体。通过功能得失实验、荧光素酶报告实验、染色质免疫沉淀实验和免疫组织化学实验，揭示结肠癌细胞与雪旺细胞之间的相互作用。此外，将与雪旺细胞共培养的结肠癌细胞移植到裸鼠体内，以评价其对肿瘤增殖和转移的影响。临床病理特征提示，许旺细胞在结肠癌组织中表达丰富，与肿瘤转移和预后不良有关。雪旺细胞与结肠癌细胞共培养可促进结肠癌细胞和雪旺细胞的增殖和迁移，这一作用是由雪旺细胞分泌的神经生长因子(NGF)介导的。结肠癌细胞释放的外体miR-21-5p抑制雪旺细胞Vhl的表达，进而稳定HIF-1α蛋白，促进神经生长因子的转录。同时，雪旺细胞来源的NGF激活了结肠癌细胞内TrkA/ERK/ELK1/ZEB1信号通路，进一步增强了外体miR-21-5p的表达。抑制NGF或miR-21-5p均可显著抑制裸鼠结肠癌移植瘤的增殖和转移。同时，miR-21-5p与结肠癌组织中NGF、p-ERK、p-ELK1、ZEB1的表达呈正相关。我们的结果提示结肠癌细胞和Schwan细胞之间存在相互通讯，促进结肠癌的增殖和转移，并确定NGF和外体miR-21-5p是治疗结肠癌的潜在靶点。网上版载有补充材料，可在10.1186/s13046-022-02556-2查阅。
Research has indicated that the emergence of Schwann cells around premalignant lesions of colon cancer might be an early indicator promoting the onset of tumorigenesis. The present study explored the communication between colon cancer cells and Schwann cells. Immunofluorescence analyses were conducted to examine the differential distribution of Schwann cells within colon cancer tissues and normal colon tissues. CCK8 assay, colony formation assay, wound healing assay, and transwell assay were performed to investigate the interaction between colon cancer cells and Schwann cells. Exosomes derived from colon cancer cells were isolated to further explore the effect of colon cancer cells on Schwann cells. Gain- and loss-of function experiments, luciferase reporter assays, chromatin immunoprecipitation assays, and immunohistochemistry assays were performed to reveal the cross-talk between colon cancer cells and Schwann cells. Furthermore, colon cancer cells co-cultured with Schwann cells were transplanted into nude mice for evaluating their effect on tumor proliferation and metastasis in vivo. The clinicopathological characteristics indicated that Schwann cells were enriched in colon cancer tissues and were associated with tumor metastasis and poor prognosis. The co-culture of Schwann cells with colon cancer cells promoted the proliferation and migration of colon cancer cells and Schwann cells, which was mediated by nerve growth factor (NGF) secreted from Schwann cells. Exosomal miR-21-5p released by colon cancer cells inhibited VHL expression in Schwann cells, which in turn stabilized the HIF-1α protein and increased the transcription of NGF. Meanwhile, the Schwann cells-derived NGF activated TrkA/ERK/ELK1/ZEB1 signaling pathway in colon cancer cells, which further enhanced the expression of exosomal miR-21-5p. Inhibition of either NGF or miR-21-5p significantly inhibited the proliferation and metastasis of transplanted colon cancer cells in nude mice. Coincidently, miR-21-5p was positively associated with the expression of NGF, p-ERK, p-ELK1, and ZEB1 in human colon cancer tissues. Our results implicated a reciprocal communication between colon cancer cells and Schwan cells that promoted the proliferation and metastasis of colon cancer, and identified NGF and exosomal miR-21-5p as potential therapeutic targets for the treatment of colon cancer. The online version contains supplementary material available at 10.1186/s13046-022-02556-2.
登录
查看更多内容
影响因子：
29
作者：
Isaac R;Reis FCG;Ying W;Olefsky JM
通讯作者：
Olefsky JM
DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
影响因子：
5.9
作者：
Chen WY;Wen YC;Lin SR;Yeh HL;Jiang KC;Chen WH;Lin YS;Zhang Q;Liew PL;Hsiao M;Huang J;Liu YN
通讯作者：
Liu YN
金纳米簇辅助 NGF siRNA 递送有效治疗胰腺癌
影响因子：
16.6
作者：
Lei Y;Tang L;Xie Y;Xianyu Y;Zhang L;Wang P;Hamada Y;Jiang K;Zheng W;Jiang X
通讯作者：
Jiang X
DOI：
10.1186/s13046-016-0395-y
发表时间：
2016-07-21
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Aloe L;Rocco ML;Balzamino BO;Micera A
通讯作者：
Micera A