Dataset Information

Dynamic changes in macrophage subtypes during lung cancer progression and metastasis at single-cell resolution.

ABSTRACT:

Background

Lung cancer remains a major global health challenge. Macrophages (Macs) are one important component of tumor microenvironments (TMEs); however, their prognostic relevance to lung cancer is currently unknown due to the complexity of their phenotypes.

Methods

In the present study, reanalysis and atlas reconstruction of downloaded single-cell RNA sequencing (scRNAseq) data were used to systematically compare the component and transcriptional changes in Mac subtypes across different stages of lung cancer.

Results

We found that with the progression of lung cancer, the proportion of alveolar macrophages (aMacs) gradually decreased, while the proportions of Macs and monocytes (Monos) gradually increased, suggesting a chemotaxis process followed by a Mono-Mac differentiation process. Meanwhile, through ligand-receptor (LR) screening, we identified 9 Mac-specific interactions that were enriched during the progression and metastasis of lung cancer, which could potential promote M2 polarization or the infiltration of M2 Macs. Moreover, we found that the expression of SPP1 in Macs increased with lung cancer progression, and identified 9 genes that were correlated with the expression of SPP1 in Macs, which might also contribute to the immunosuppression process in lung cancer.

Conclusions

Our results revealed detailed changes in Macs at different stages of lung cancer progression and metastasis and provided potential therapeutic targets that could be used in future lung cancer treatments.

SUBMITTER: Wang J

PROVIDER: S-EPMC10482613 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Dynamic changes in macrophage subtypes during lung cancer progression and metastasis at single-cell resolution.

Wang Jian J Wu Weiqing W Xia Jinquan J Chen Lipeng L Liu Dongcheng D Wang Guangsuo G Wang Lingwei L Zheng Qijun Q

Journal of thoracic disease 20230828 8

<h4>Background</h4>Lung cancer remains a major global health challenge. Macrophages (Macs) are one important component of tumor microenvironments (TMEs); however, their prognostic relevance to lung cancer is currently unknown due to the complexity of their phenotypes.<h4>Methods</h4>In the present study, reanalysis and atlas reconstruction of downloaded single-cell RNA sequencing (scRNAseq) data were used to systematically compare the component and transcriptional changes in Mac subtypes across ...[more]

PMID: 37691661

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Project description:BackgroundAccumulating evidence suggests that M2-polarized tumor-associated macrophages (TAMs) play an important role in cancer progression and metastasis, making M2 polarization of TAMs an ever more appealing target for therapeutic intervention. Astragaloside IV (AS-IV), a saponin component isolated from Astragali radix, has been reported to inhibit the invasion and metastasis of lung cancer, but its effects on TAMs during lung cancer progression have not been investigated.MethodsHuman THP-1 monocytes were induced to differentiate into M2 macrophages through treatments with IL-4, IL-13, and phorbol myristate acetate (PMA). We used the lung cancer cell lines A549 and H1299 cultured in conditioned medium from M2 macrophages (M2-CM) to investigate the effects of AS-IV on tumor growth, invasion, migration, and angiogenesis of lung cancer cells. Macrophage subset distribution, M1 and M2 macrophage-associated markers, and mRNA expression were analyzed by flow cytometry and quantitative PCR. The activation of adenosine monophosphate-activated protein kinase (AMPK) signaling pathways that mediate M2-CM-promoted tumor migration was detected using western blotting.ResultsHere we found that AS-IV significantly inhibited IL-13 and IL-4-induced M2 polarization of macrophages, as illustrated by reduced expression of CD206 and M2-associated genes, and that AS-IV suppressed the M2-CM-induced invasion, migration, and angiogenesis of A549 and H1299 cells. In vivo experiments demonstrated that AS-IV greatly inhibited tumor growth and reduced the number of metastases of Lewis lung cancer. The percentage of M2 macrophages was decreased in tumor tissue after AS-IV treatment. Furthermore, AS-IV inhibited AMPKα activation in M2 macrophages, and silencing of AMPKα partially abrogated the inhibitory effect of AS-IV.ConclusionsAS-IV reduced the growth, invasion, migration, and angiogenesis of lung cancer by blocking the M2 polarization of macrophages partially through the AMPK signaling pathway, which appears to play an important role in AS-IV's ability to inhibit the metastasis of lung cancer.

Dataset Information

Dynamic changes in macrophage subtypes during lung cancer progression and metastasis at single-cell resolution.

Background

Methods

Results

Conclusions

Publications

Dynamic changes in macrophage subtypes during lung cancer progression and metastasis at single-cell resolution.

Similar Datasets

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