Legumain Promotes Gastric Cancer Progression Through Tumor-associated Macrophages <i>In vitro</i> and <i>In vivo</i>

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 <i>in vitro,</i> while downregulation of LGMN expression reduced cell proliferation, migration and invasion. <i>In vivo</i> 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<i>,</i> which may serve as a potential target for GC treatment, promoted gastric cancer cell proliferation and angiogenesis <i>in vitro</i> and <i>in vivo</i>.