Gallbladder cancer-associated fibroblasts promote the migration of lymphatic endothelial cells via releasing IGFBP3

Rui ZHANG; Chen CHEN; Huwei SONG; Qi LI; Dong ZHANG; Wenzhi LI; Lin WANG; Zhimin GENG

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Gallbladder cancer-associated fibroblasts promote the migration of lymphatic endothelial cells via releasing IGFBP3

VernacularTitle:胆囊癌相关成纤维细胞分泌IGFBP3促进淋巴内皮细胞的迁移
Author: Rui ZHANG ¹ ; Chen CHEN ¹ ; Huwei SONG ¹ ; Qi LI ¹ ; Dong ZHANG ¹ ; Wenzhi LI ¹ ; Lin WANG ² ; Zhimin GENG ¹
Author Information

1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
2. Department of Geriatric Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
Publication Type:Journal Article
Keywords: gallbladder carcinoma; cancer-associated fibroblast; lymphatic endothelial cell; cell migration; insulin-like growth factor binding protein 3 (IGFBP3)
From: Journal of Xi'an Jiaotong University(Medical Sciences) 2021;42(1):11-17,29
CountryChina
Language:Chinese
Abstract: 【Objective】 To investigate the effects of gallbladder cancer-associated fibroblasts (CAFs) on the migration of lymphatic endothelial cells (LECs) so as to elucidate the molecular mechanisms involved. 【Methods】 The CAFs and normal fibroblasts (NFs) were extracted by enzymatic digestion, and the supernatant (CM) of CAFs and NFs was collected. The levels of IL-6, IGFBP3 and other related cytokines were detected by semi-quantitative protein factor microarray and ELISA. The expressions of α-SMA (CAFs maker) and IGFBP3 in gallbladder cancer and para-cancer tissues were detected by immunohistochemistry, and the correlation of α-SMA and IGFBP3 expressions with clinicopathological characteristics were analyzed. LECs were cultured and divided into serum-free medium group (control group), CAF-CM co-culture group, NF-CM co-culture group, IGFBP3 group, and CAF-CM+IGFBP3 inhibitor (2-Deoxy-D-glucose, 2-DG) group according to different treatment. Transwell migration assays and wound healing assays were applied to analyze the migration ability of LECs under different treatment. The expressions of E-cadherin, N-cadherin and Vimentin were detected by Western blotting. 【Results】 Protein factor microarray and ELISA showed that the concentration of IGFBP3 in CAF-CM was significantly increased, and the expression of α-SMA was significantly related to lymph node metastasis, advanced TNM stage and expression of IGFBP3. IGFBP3 secreted from CAF-CM significantly promoted LECs migration, up-regulated the expression of N-cadherin and Vimentin, and down-regulated the expression of E-cadherin. Treatment with IGFBP3 inhibitor 2-DG could reverse the effect of CAF-CM on migration of LECs and related protein expressions. 【Conclusion】 Gallbladder CAFs promote the migration of LECs via releasing IGFBP3, which affects EMT transformation.