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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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202406865 |
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| author | Lei Song Xi Yu Yang Wu Wenwen Zhang Yu Zhang Yanchi Shao Zhenxin Hou Chen Yang Yue Gao Yanbin Zhao |
| author_facet | Lei Song Xi Yu Yang Wu Wenwen Zhang Yu Zhang Yanchi Shao Zhenxin Hou Chen Yang Yue Gao Yanbin Zhao |
| author_sort | Lei Song |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a6eae0340dce447bb3535b686a3ca853 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-a6eae0340dce447bb3535b686a3ca8532025-01-13T15:29:43ZengWileyAdvanced Science2198-38442025-01-01122n/an/a10.1002/advs.202406865Integrin β8 Facilitates Macrophage Infiltration and Polarization by Regulating CCL5 to Promote LUAD ProgressionLei Song0Xi Yu1Yang Wu2Wenwen Zhang3Yu Zhang4Yanchi Shao5Zhenxin Hou6Chen Yang7Yue Gao8Yanbin Zhao9Department of Internal Medical Oncology Harbin Medical University Cancer Hospital Harbin Heilongjiang 150081 ChinaDepartment of Gynecological Oncology Harbin Medical University Cancer Hospital Harbin Heilongjiang 150081 ChinaDepartment of Breast Surgery Harbin Medical University Cancer Hospital Harbin Heilongjiang 150081 ChinaDepartment of Gynecological Oncology Harbin Medical University Cancer Hospital Harbin Heilongjiang 150081 ChinaDepartment of Internal Medical Oncology Harbin Medical University Cancer Hospital Harbin Heilongjiang 150081 ChinaDepartment of Internal Medical Oncology Harbin Medical University Cancer Hospital Harbin Heilongjiang 150081 ChinaDepartment of Internal Medical Oncology Harbin Medical University Cancer Hospital Harbin Heilongjiang 150081 ChinaDepartment of Internal Medical Oncology Harbin Medical University Cancer Hospital Harbin Heilongjiang 150081 ChinaCollege of Bioinformatics Science and Technology Harbin Medical University Harbin Heilongjiang 150081 ChinaDepartment of Internal Medical Oncology Harbin Medical University Cancer Hospital Harbin Heilongjiang 150081 ChinaAbstract 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.https://doi.org/10.1002/advs.202406865CCL5ITGβ8LUADmacrophageTME |
| spellingShingle | Lei Song Xi Yu Yang Wu Wenwen Zhang Yu Zhang Yanchi Shao Zhenxin Hou Chen Yang Yue Gao Yanbin Zhao Integrin β8 Facilitates Macrophage Infiltration and Polarization by Regulating CCL5 to Promote LUAD Progression Advanced Science CCL5 ITGβ8 LUAD macrophage TME |
| title | Integrin β8 Facilitates Macrophage Infiltration and Polarization by Regulating CCL5 to Promote LUAD Progression |
| title_full | Integrin β8 Facilitates Macrophage Infiltration and Polarization by Regulating CCL5 to Promote LUAD Progression |
| title_fullStr | Integrin β8 Facilitates Macrophage Infiltration and Polarization by Regulating CCL5 to Promote LUAD Progression |
| title_full_unstemmed | Integrin β8 Facilitates Macrophage Infiltration and Polarization by Regulating CCL5 to Promote LUAD Progression |
| title_short | Integrin β8 Facilitates Macrophage Infiltration and Polarization by Regulating CCL5 to Promote LUAD Progression |
| title_sort | integrin β8 facilitates macrophage infiltration and polarization by regulating ccl5 to promote luad progression |
| topic | CCL5 ITGβ8 LUAD macrophage TME |
| url | https://doi.org/10.1002/advs.202406865 |
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