Modulation the crosstalk between tumor-associated macrophages and non-small cell lung cancer to inhibit tumor migration and invasion by ginsenoside Rh2

Li, Honglin; Huang, Nan; Zhu, Weikang; Wu, Jianchun; Yang, Xiaohui; Teng, Wenjing; Tian, Jie; Fang, Zhihong; Luo, Yingbin; Chen, Min; Li, Yan

doi:10.1186/s12885-018-4299-4

Cited by 134 publications

(99 citation statements)

References 41 publications

(53 reference statements)

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“…All cell lines were obtained from ATCC, grown at 37°C with 5% CO 2 , and STR verified yearly by ATCC. THP-1 cells (a human monocytic cell line) represent an established in vitro model commonly used to examine TAM-tumor cells interactions [ 15 ]. AsPC-1 cells were cultured in modified RPMI 1640 containing 10% FBS, 10 mM HEPES, 1 mM sodium pyruvate, and 13.9 mM D-glucose.…”

Section: Methodsmentioning

confidence: 99%

Tumor-promoting effects of pancreatic cancer cell exosomes on THP-1-derived macrophages

et al. 2018

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Pancreatic ductal adenocarcinoma (PDAC) tumor growth is enhanced by tumor-associated macrophages (TAMs), yet the mechanisms by which tumor cells and TAMs communicate are not fully understood. Here we show that exosomes secreted by PDAC cell lines differed in their surface proteins, lipid composition, and efficiency of fusing with THP-1-derived macrophages in vitro. Exosomes from AsPC-1, an ascites-derived human PDAC cell line, were enriched in ICAM-1, which mediated their docking to macrophages through interactions with surface-exposed CD11c on macrophages. AsPC-1 exosomes also contained much higher levels of arachidonic acid (AA), and they fused at a higher rate with THP-1-derived macrophages than did exosomes from other PDAC cell lines or from an immortalized normal pancreatic ductal epithelial cell line (HPDE) H6c7. Phospholipase A2 enzymatic cleavage of arachidonic acid from AsPC-1 exosomes reduced fusion efficiency. PGE2 secretion was elevated in macrophages treated with AsPC-1 exosomes but not in macrophages treated with exosomes from other cell lines, suggesting a functional role for the AsPC-1 exosome-delivered arachidonic acid in macrophages. Non-polarized (M0) macrophages treated with AsPC-1 exosomes had increased levels of surface markers indicative of polarization to an immunosuppressive M2-like phenotype (CD14hi CD163hi CD206hi). Furthermore, macrophages treated with AsPC-1 exosomes had significantly increased secretion of pro-tumoral, bioactive molecules including VEGF, MCP-1, IL-6, IL-1β, MMP-9, and TNFα. Together, these results demonstrate that compared to exosomes from other primary tumor-derived PDAC cell lines, AsPC-1 exosomes alter THP-1-derived macrophage phenotype and function. AsPC-1 exosomes mediate communication between tumor cells and TAMs that contributes to tumor progression.

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Section: Methodsmentioning

confidence: 99%

Tumor-promoting effects of pancreatic cancer cell exosomes on THP-1-derived macrophages

et al. 2018

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“…Although various biomolecules have been found to mediate lung cancer metastasis, knowledge regarding to roles of tumor microenvironment in lung cancer metastasis has largely lagged behind. Stromal cells including TAMs in the tumor microenvironment are either induced or directly interacting with cancer cells to promote the progression and metastasis of lung cancer [33,34] . The modes of action of stromal cells include the secretion of extracellular components, such as growth factors, chemokines and exosomes.…”

Section: Discussionmentioning

confidence: 99%

Tumor-Associated Macrophages Secret Exosomal miR-155 to Promote Metastasis of Non-Small-Cell Lung Cancer

Chen

et al. 2020

Preprint

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Background: Understanding the molecular basis underlying metastasis of non-small-cell lung cancer (NSCLC) may provide new therapeutic modality for the treatment of NSCLC. However, the mechanisms by which tumor-associated macrophages (TAMs) affect NSCLC metastasis still remain undefined.Methods: The role of macrophages in NSCLC was elucidated by gene set enrichment analysis via The Cancer Genome Atlas database (TCGA) database, and we further verified it through Quantitative real-time PCR and immunohistochemical staining. Exosomes from TAMs were extracted and co-cultured with A549 cells,the biological functions of miR-155 were evaluated through miRNAs sequencing, transwell assays,western blotting,fluorescence labeling,luciferase reporter assay, and animal experiments.Results: We found that M2 TAMs are abundant in metastatic tissues of NSCLC patients and exosomes secreted by M2 TAMs promote epithelial mesenchymal transition(EMT) and migration of A549 cells.Mechanistically,we demonstrated that miR-155 is the biomolecule in exosomes secreted by M2 TAMs and targets 3’-untranslated regions (UTRs) of RASSF4 to promote NSCLC metastasis.Conclusions: MiR-155 is the key functional molecule in M2 TAMs-released exosomes that promote EMT of NSCLC cells through targeting RASSF4. Our study suggests that miR-155 in TAMs and exosomes may serve as a novel therapeutic target in the treatment of lung cancer.

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“…Stromal cells including TAMs in the tumor microenvironment are either induced or directly interacting with cancer cells to promote the progression and metastasis of lung cancer. [30,31] The modes of action of stromal cells including the secretion of extracellular components, such as growth factors, chemokines and exosomes. However, due to the extreme complexity of these processes, the molecular mechanisms underlying lung metastasis has not been fully understood.…”

Section: Discussionmentioning

confidence: 99%

Tumor-associated macrophages secret exosomal miR-155 to promote metastasis of non-small-cell lung cancer

Chen

et al. 2020

Preprint

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Background: Understanding the molecular basis underlying metastasis of non-small-cell lung cancer (NSCLC) may provide new therapeutic modality for treatment of NSCLC. However, the mechanisms by which tumor-associated macrophages (TAMs) affect NSCLC metastasis still remain undefined. Method: Phenotype of TAMs was identified by flow cytometry. The migration of the tumor cells was detected by transwell assay. Transmission electron microscopy (TEM) and PKH-67 was used to identified and label the exosome. Expression of miR-155 was measured by qRT-PCR. Luciferase analysis, western blot, and rescue assay were used to investigate potential mechanisms of miR-155.Results: We discovered a novel regulatory pathway involved in NSCLC metastasis. We found that M2 TAMs were the main TAMs in metastatic tissues of NSCLC patients and exosomes derived from M2 TAMs were able to promote epithelial-mesenchymal transition (EMT) and migration of NSCLC cells. We demonstrated that miR-155 was abundant in M2 TAMs and exosomes secreted by M2 TAMs. Moreover, we also verified that miR-155 was the key functional biomolecule in exosomes secreted by M2 TAMs. Furthermore, we confirmed that deletion of miR-155 in M2 TAMs could significantly prevent NSCLC metastasis. Overall, Conclusions: we revealed a new regulatory pathway that is M2 TAMs secret exosomal miR-155 to promote NSCLC metastasis. Our findings may provide a practical target for treatment of NSCLC.

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Modulation the crosstalk between tumor-associated macrophages and non-small cell lung cancer to inhibit tumor migration and invasion by ginsenoside Rh2

Cited by 134 publications

References 41 publications

Tumor-promoting effects of pancreatic cancer cell exosomes on THP-1-derived macrophages

Tumor-promoting effects of pancreatic cancer cell exosomes on THP-1-derived macrophages

Tumor-Associated Macrophages Secret Exosomal miR-155 to Promote Metastasis of Non-Small-Cell Lung Cancer

Tumor-associated macrophages secret exosomal miR-155 to promote metastasis of non-small-cell lung cancer

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