Department of Colorectal and Anal Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Cancer Res Treat. 2019 Jan;51(1):252-266. doi: 10.4143/crt.2017.613. Epub 2018 Apr 25.
We investigated the role of tumor-associated macrophages (TAMs) on the epithelial to mesenchymal transition (EMT) of colorectal cancer cells and determined the potential mechanism involved in the metastatic process.
In this study, flow cytometry was used to detect the expression of target proteins. We used transwell assay to evaluate the migration of cancer cells under specific conditions. Using real-time polymerase chain reaction, we examined the expressions of cytokines and EMT-related markers in mRNA level. Animal assay was performed for analysis in vivo and hematoxylin and eosin was used to visualize the effect of TAMs on tumor metastasis. We also used immunohistochemistry and Western blotting to detect the expression of target proteins.
Here, we observed enrichment of TAMs in colorectal tumor tissues, resulting in high metastasis in clinical therapy. Moreover, those TAMs could facilitate the EMT progression of colorectal cancer cells, which is induced by the transforming growth factor-β (TGF-β) derived from TAMs, leading to the invasion and migration of cancer cells.
Our results demonstrated that TAMs contributed the EMT progression through a TGF-β/Smad2,3-4/Snail signaling pathway, and disrupting this pathway with TGF-β receptor inhibitor could suppress metastasis, readjusting our focus to the connection of TAMs and cancer metastasis.
本研究旨在探讨肿瘤相关巨噬细胞（TAMs）在结直肠癌细胞上皮间质转化（EMT）中的作用，并确定其在转移过程中涉及的潜在机制。
在本研究中，采用流式细胞术检测靶蛋白的表达。我们使用 Transwell 实验来评估在特定条件下癌细胞的迁移能力。通过实时聚合酶链反应，我们检测了细胞因子和 EMT 相关标志物在 mRNA 水平上的表达。通过动物实验进行体内分析，并用苏木精和伊红染色观察 TAMs 对肿瘤转移的影响。我们还使用免疫组织化学和 Western blot 检测了靶蛋白的表达。
本研究观察到 TAMs 在结直肠肿瘤组织中的富集，导致临床治疗中的高转移率。此外，这些 TAMs 可以促进结直肠癌细胞的 EMT 进展，这是由 TAMs 衍生的转化生长因子-β（TGF-β）诱导的，导致癌细胞的侵袭和迁移。
我们的研究结果表明，TAMs 通过 TGF-β/Smad2、3、4/Snail 信号通路促进 EMT 进展，通过 TGF-β 受体抑制剂阻断该通路可抑制转移，从而重新关注 TAMs 与癌症转移之间的联系。
