Integrin β8 Facilitates Macrophage Infiltration and Polarization by Regulating CCL5 to Promote LUAD Progression

Integrin β8 Facilitates Macrophage Infiltration and Polarization by Regulating CCL5 to Promote LUAD Progression

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...

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Bibliographic Details
Main Authors: Lei Song, Xi Yu, Yang Wu, Wenwen Zhang, Yu Zhang, Yanchi Shao, Zhenxin Hou, Chen Yang, Yue Gao, Yanbin Zhao
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Advanced Science
Subjects:
CCL5
ITGβ8
LUAD
macrophage
TME
Online Access:https://doi.org/10.1002/advs.202406865
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Summary: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.
ISSN:2198-3844

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