Tumor‐associated macrophages promote the metastasis and growth of non‐small‐cell lung cancer cells through NF‐κB/PP2Ac‐positive feedback loop

Liang, Zhan-Wen; Ge, Xin-Xin; Xu, Mengdan; Qin, Hualong; Wu, Mengyao; Shen, Meng‐Ru; Zhang, Yan; Liu, Xiaomeng; Chen, Kai; Li, Wei; Duan, Weiming; Qin, Songbing

doi:10.1111/cas.14863

Cited by 20 publications

(17 citation statements)

References 57 publications

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“… 48 Many studies have reported that the invasion and metastasis of NSCLC are closely related to its microenvironment. 49 However, the link between the metastasis of NSCLC and macrophages and the underlying molecular mechanism have not yet been clarified.…”

Section: Discussionmentioning

confidence: 99%

M2‐like macrophage‐derived exosomes facilitate metastasis in non‐small‐cell lung cancer by delivering integrin αVβ3

Huang

Wang

et al. 2022

MedComm

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Metastasis is the most prevalent cause of cancer deaths, and immunological components of the tumor microenvironment, especially tumor‐associated macrophages (TAMs), play a vital role in cancer metastasis. However, the underlying mechanisms of TAMs on non‐small‐cell lung cancer (NSCLC) metastasis remain largely unexplored. Herein, we demonstrated that M2‐like TAMs facilitate the migration and invasion of cancer cells in vitro and in vivo through intercellular delivery of M2‐like macrophage‐derived exosomes (M2‐exos). Importantly, we found that M2‐exos had considerably higher levels of integrin (ITG) αV and β3. The impact of M2‐like macrophage‐mediated invasion and migration of NSCLC cells was clearly decreased when ITG αVβ3 was blocked. Mechanistically, exosomal ITG αVβ3 produced from M2‐like macrophages successfully triggered the focal adhesion kinase signaling pathway in recipient cells, boosting the migratory and invasive abilities of NSCLC cells. Clinically, we found that metastatic NSCLC patients had greater ITG αV and β3 expression, which was associated with a worse prognosis. This study reveals a novel mechanism by which M2‐exos significantly increased NSCLC cell migration and invasion by delivering integrin αVβ3. Exosomal ITG αVβ3 can be used as a potential prognostic marker, and blocking ITG αVβ3 could be a viable treatment option for preventing tumor metastasis.

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Section: Discussionmentioning

confidence: 99%

M2‐like macrophage‐derived exosomes facilitate metastasis in non‐small‐cell lung cancer by delivering integrin αVβ3

Huang

Wang

et al. 2022

MedComm

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show abstract

“…2 Lung cancer cells can interact with immune cells and alter immune cell phenotypes that may contribute to the establishment of a tumor-supporting environment, which indicates resistance to cancer therapy. 3 As one of the main regulatory components in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are especially important in lung cancer, given their significant correlation with cancer growth, metastasis, patient prognosis, [4][5][6] and chemotherapy resistance. 7 Previous studies have suggested that TAMs can be functionally subtyped according to polarization status, namely M1-like and M2-like, and further demonstrated that M2-like TAMs play a tumorsupportive role in lung cancer.…”

Section: Introductionmentioning

confidence: 99%

“… 2 Lung cancer cells can interact with immune cells and alter immune cell phenotypes that may contribute to the establishment of a tumor‐supporting environment, which indicates resistance to cancer therapy. 3 As one of the main regulatory components in the tumor microenvironment (TME), tumor‐associated macrophages (TAMs) are especially important in lung cancer, given their significant correlation with cancer growth, metastasis, patient prognosis, 4 , 5 , 6 and chemotherapy resistance. 7 …”

Section: Introductionmentioning

confidence: 99%

Depletion of tumor‐associated macrophages inhibits lung cancer growth and enhances the antitumor effect of cisplatin

et al. 2022

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In lung cancer, tumor-associated macrophages (TAMs), especially M2-like TAMs, represent the main tumor progression components in the tumor microenvironment (TME). Therefore, M2-like TAMs may serve as a therapeutic target. The purpose of this study was to investigate the effect of M2-like TAM depletion in the TME on tumor growth and chemotherapy response in lung cancer. The levels of secreted monocyte chemoattractant protein (MCP-1) and prostaglandin E2 (PGE2) in the supernatants of lung cancer cell lines A549 and LLC were evaluated via ELISA. Cell migration assays were performed to assess the recruitment ability of macrophage cell lines THP-1 and J774-1 cells. Differentiation of macrophages was assessed via flow cytometry. Immunohistochemical staining was performed to visualize M2-like TAMs in transplanted lung cancer in mouse. We used the COX-2 inhibitor nimesulide to inhibit the secretion of MCP-1 and PGE2, which promotes macrophage migration and M2-like differentiation. Nimesulide treatment decreased the secretion of MCP-1 and PGE2 from lung cancer cells. Nimesulide treatment suppressed the migration of macrophages by blocking MCP-1. Lung cancer supernatant induced the differentiation of macrophages toward the M2-like phenotype, and nimesulide treatment inhibited M2-like differentiation by blocking MCP-1 and PGE2. In the lung cancer mouse model, treatment with nimesulide depleted M2-like TAMs in the TME and enhanced the tumor inhibitory effect of cisplatin. Our results indicated that blocking the secretion of MCP-1 and PGE2 from tumor cells depleted M2-like TAMs in the TME and the combination therapy with cisplatin considerably suppressed tumor growth in the LLC mouse model.

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“…They can be "domesticated" by tumour cells to polarize toward M2-like macrophages phenotype, therefore supporting tumour progression [49]. Many studies have reported that the invasion and metastasis of NSCLC is closely related to its microenvironment [50]. However, the link between the metastasis of NSCLC and M2 macrophages and the underlying molecular mechanism have not yet been clari ed.…”

Section: Discussionmentioning

confidence: 99%

M2 Macrophage -Derived Exosomefacilitates Metastasis in Non-Small-Cell Lung Cancer via Delivering Integrin αvβ3

et al. 2022

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Tumor‐associated macrophages promote the metastasis and growth of non‐small‐cell lung cancer cells through NF‐κB/PP2Ac‐positive feedback loop

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 20 publications

References 57 publications

M2‐like macrophage‐derived exosomes facilitate metastasis in non‐small‐cell lung cancer by delivering integrin αVβ3

M2‐like macrophage‐derived exosomes facilitate metastasis in non‐small‐cell lung cancer by delivering integrin αVβ3

Depletion of tumor‐associated macrophages inhibits lung cancer growth and enhances the antitumor effect of cisplatin

M2 Macrophage -Derived Exosomefacilitates Metastasis in Non-Small-Cell Lung Cancer via Delivering Integrin αvβ3

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