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Integrin β8 Facilitates Macrophage Infiltration and Polarization by Regulating CCL5 to Promote LUAD Progression
1Department of Internal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, China.
Abstract:
The tumor microenvironment (TME) influences cancer progression and metastasis. Integrin β8 (ITGβ8), a member of the integrin family, is upregulated in various cancers. In this study, it is determined as a key factor that mediates the interaction between lung adenocarcinoma (LUAD) cells and macrophages. Increased expression levels of ITGβ8 are associated with increased numbers of CD163+ macrophages and poor prognosis in LUAD patients. The overexpression of ITGβ8 in LUAD cells promotes the polarization of THP-1 macrophages toward the M2 phenotype. In contrast, TCM (conditioned medium from the co-culture system) from THP-1 macrophages and ITGβ8-overexpressing A549 cells promoted the proliferation and invasion of A549 cells. Mechanistically, chemokine (C-C motif) ligand 5 (CCL5) plays an important role in mediating ITGβ8-induced macrophage polarization, and the phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT)/interferon regulatory factor 9 (IRF9) pathway is involved in this process. Moreover, interleukin 8 (IL8) and interleukin 10 (IL10) produced by M2-like macrophages regulate the expression of ITGβ8 in LUAD cells through the spi-1 proto-oncogene (SPI1). This study elucidates the feedback mechanism of ITGβ8 between LUAD cells and macrophages.
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