Abstract: Objective To investigate the effects of M2⁃type tumor⁃associated macrophages (TAMs) on the proliferation of gastric cancer cells and epithelial⁃mesenchymal transition (EMT) , along with possible mechanisms. Methods THP⁃1 cells were differentiated into M2⁃type macrophages in vitro and treated with conditioned medium from gastric cancer MKN⁃45 cells to obtain M2⁃type TAMs (M2⁃TAMs). M2⁃TAMs were co⁃cultured with MKN⁃45 cells (MKN⁃45 group and M2⁃TAMs/MKN⁃45 group). In addition, siRNA technology was used to silence collagen triple helix repeat containing 1 (CTHRC1) in MKN⁃45 cells, the cells were co⁃cultured with or without M2⁃TAMs (si⁃NC group, si⁃CTHRC1 group, M2⁃TAMs/si⁃NC group, and M2⁃TAMs/si⁃CTHRC1 group). Cell proliferation, invasion and migration abilities were detected by CCK⁃8, colony formation, Transwell and scratch test. The levels of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) in cell supernatant were detected by ELISA. qRT⁃PCR was used to detect the expression level of CTHRC1 mRNA in cells. Western blot was used to detect the protein expression levels of E⁃cadherin, N⁃cadherin, Vimentin and CTHRC1. Results Compared with the MKN⁃45 group, the M2⁃TAMs/MKN⁃45 group showed significantly increased cell proliferation, migration and invasion abilities (all P<0.05), upregulated MMP2 and MMP9 levels (all P<0.01), decreased E⁃cadherin expression(P<0.001), and increased N⁃cadherin, Vimentin and CTHRC1 expression (all P<0.01). Compared with the si⁃NC group, the si⁃CTHRC1 group exhibited significantly reduced cell proliferation, migration and invasion abilities (all P<0.05), increased E⁃cadherin expression (P<0.001), and decreased CTHRC1, N⁃cadherin and Vimentin expression (all P<0.01). Compared with the M2⁃TAMs/si⁃NC group, the M2⁃TAMs/si⁃CTHRC1 group showed significantly decreased cell proliferation, migration and invasion abilities (all P<0.05), increased E⁃cadherin expression (P<0.001), and decreased CTHRC1, N⁃cadherin and Vimentin expression (all P<0.01). Conclusions M2⁃type TAMs may promote the proliferation and EMT of gastric cancer MKN⁃45 cells by upregulating CTHRC1 expression.

Key words: Tumor?associated macrophages, Gastric cancer, Collagen triple helix repeat containing 1, Proliferation, Epithelial?mesenchymal transition