Int J Biol Sci 2020; 16(1):172-180. doi:10.7150/ijbs.36467

Research Paper

Legumain Promotes Gastric Cancer Progression Through Tumor-associated Macrophages In vitro and In vivo

Hongbin Wang1,2, Binghong Chen3, Yingying Lin3, Yi Zhou1, Xiaobo Li1✉

1. Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
2. Department of Gastroenterology, Punan Hospital, Pudong New Area, Shanghai, China.
3. Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

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Citation:
Wang H, Chen B, Lin Y, Zhou Y, Li X. Legumain Promotes Gastric Cancer Progression Through Tumor-associated Macrophages In vitro and In vivo. Int J Biol Sci 2020; 16(1):172-180. doi:10.7150/ijbs.36467. Available from http://www.ijbs.com/v16p0172.htm

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Abstract

Tumor-associated macrophages (TAMs) play a crucial role in the tumor microenvironment. Legumain (LGMN) has been shown to be a tumor-promoting protein, but the effect of LGMN on TAMs in the progression of gastric cancer (GC) is under exploration. Our studies included the construction of LGMN-knockdown and LGMN-overexpressing TAMs induced from the human cell line THP-1 (PMA/IL-4/IL-13) and murine cell line Raw264.7 (IL-4/IL-13). A CCK-8 assay and transwell migration assay indicated that upregulation of LGMN expression in TAMs stimulated cell proliferation, migration and invasion in vitro, while downregulation of LGMN expression reduced cell proliferation, migration and invasion. In vivo experiments revealed slower growth, less angiogenesis, and less Ki67 expression in LGMN-knockdown TAMs injected with gastric cancer cells compared to control TAMs injected with GC cells. Together, these study results suggested that LGMN+ TAMs, which may serve as a potential target for GC treatment, promoted gastric cancer cell proliferation and angiogenesis in vitro and in vivo.

Keywords: Legumain, gastric cancer, tumor-associated macrophages, angiogenesis