Department of Gastrointestinal Surgery, Taizhou Clinical Medical School of Nanjing Medical University (Taizhou People's Hospital), Taizhou 225300, Jiangsu, China.
Department of Clinical Speciality, Nanjing Medical University, Nanjing 210009, Jiangsu, China.
Aging (Albany NY). 2021 Jul 14;13(14):18464-18481. doi: 10.18632/aging.203295.
Background The gastric cancer (GC) microenvironment has important effects on biological behaviors, such as tumor cell invasion and metastasis. However, the mechanism by which the GC microenvironment promotes GC cell invasion and metastasis is unknown. The present study aimed to clarify the effects and mechanism of galectin-1 (GAL-1, encoded by ) on GC invasion and metastasis in the GC microenvironment. Methods The expression of GAL-1/ was determined using western blotting, immunohistochemistry, and quantitative real-time reverse transcription PCR in GC tissues. Besides, methods including stable transfection, Matrigel invasion and migration assays, and wound-healing assays ; and metastasis assays , were also conducted. Results GAL-1 from cancer-associated fibroblasts (CAFs) induced the epithelial-mesenchymal transition (EMT) of GC cells though the transforming growth factor beta (TGF-β1)/ Sma- and mad-related protein (Smad) pathway, and affected the prognosis of patients with GC. The level of GAL-1 was high in CAFs, and treating MGC-803 and SGC -7901 cell line with the conditioned medium from CAFs promoted their invasion and metastasis abilities. Overexpression of promoted the expression of TGF-β1 and induced EMT of GC cell lines. A TGF-β1 antagonist inhibited the invasion and migration of GC cells. , overexpression of promoted GC growth and metastasis, and the TGF-β1 antagonist dramatically reversed these events. Conclusions These findings suggested that high expression of GAL-1 in the GC microenvironment predicts a poor prognosis in patients with GC by promoting the migration and invasion of GC cells via EMT through the TGF-β1/Smad signaling pathway. The results might provide new therapeutic targets to treat GC.
胃癌（GC）微环境对肿瘤细胞的侵袭和转移等生物学行为有重要影响。然而，GC 微环境促进 GC 细胞侵袭和转移的机制尚不清楚。本研究旨在阐明半乳糖凝集素-1（GAL-1，由 编码）在 GC 微环境中对 GC 细胞侵袭和转移的影响及其机制。
采用 Western blot、免疫组织化学和实时定量逆转录 PCR 检测 GC 组织中 GAL-1/ 的表达。此外，还进行了稳定转染、Matrigel 侵袭和迁移实验以及划痕愈合实验；以及转移实验。
来自癌相关成纤维细胞（CAFs）的 GAL-1 通过转化生长因子-β（TGF-β1）/Smad 途径诱导 GC 细胞发生上皮间质转化（EMT），并影响 GC 患者的预后。CAFs 中 GAL-1 水平较高，用 CAFs 的条件培养基处理 MGC-803 和 SGC-7901 细胞系可促进其侵袭和转移能力。过表达 可促进 TGF-β1 的表达并诱导 GC 细胞系发生 EMT。TGF-β1 拮抗剂抑制 GC 细胞的侵袭和迁移。过表达 可促进 GC 的生长和转移，而 TGF-β1 拮抗剂则显著逆转这些事件。
GC 微环境中 GAL-1 的高表达通过 TGF-β1/Smad 信号通路促进 EMT，从而预测 GC 患者预后不良。这些发现可能为治疗 GC 提供新的治疗靶点。
