Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration

Zhang, Xu; Shi, Hui; Yuan, Xiuhua; Jiang, Pengcheng; Qian, Hui; Xu, Wenrong

doi:10.1186/s12943-018-0898-6

Cited by 243 publications

(213 citation statements)

References 56 publications

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“…In addition to TAM, fibroblasts, dendritic cells, epithelial cells, neutrophils, and lymphocytes can also be tamed by tumor cells and promote a tumor malignant environment. [53][54][55][56][57][58] It has been reported that dendritic cells, fibroblasts, and epithelial cells tamed by cancer cells secrete CCL2. [55][56][57][58]…”

Section: Discussionmentioning

confidence: 99%

Tumor‐associated macrophages secrete CC‐chemokine ligand 2 and induce tamoxifen resistance by activating PI3K/Akt/mTOR in breast cancer

et al. 2019

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Abbreviations: CCL2, CC-chemokine ligand 2; CM, conditioned medium; ER, estrogen receptor; MCP-1, monocyte chemoattractant protein 1; MR, tumor-associated macrophage from a tamoxifen-resistant tumor microenvironment; MS, tumor-associated macrophage from a tamoxifen-sensitive tumor microenvironment; PFS, progression-free survival; TAM, tumor-associated macrophage; TME, tumor microenvironment. AbstractBreast cancer is the most prevalent malignancy among women. Although endocrine therapy is effective, the development of endocrine resistance is a major clinical challenge. The tumor microenvironment (TME) promotes tumor malignancy, and tumor-associated macrophages (TAM) within the TME play a crucial role in endocrine resistance. Herein, we aimed to elucidate the relationship between TAM and the endocrine-resistant phenotype of breast cancer. Macrophages were cultured with conditioned medium (CM) from tamoxifen-sensitive (MCF7-S) or -resistant (MCF7-R) MCF7 breast cancer cells. M2 polarization was detected by CD163 immunofluorescence. To determine the effect on endocrine resistance, MCF7 cells were cultured in the supernatant of different TAM, and then treated with tamoxifen. CC-chemokine ligand 2 (CCL2) immunohistochemistry was carried out on pathological sections from 100 patients with invasive estrogen receptor-positive breast cancer. We found that macrophages cultured in the CM of MCF7-S and MCF7-R cells were induced into TAM, with a more obvious M2 polarization in the latter. Tamoxifen resistance was increased by culture in TAM medium. TAM secreted CCL2, which increased endocrine resistance in breast cancer cells through activation of the PI3K/Akt/mTOR signaling pathway. High expression of CCL2 was correlated with infiltration of CD163+macrophages (r = 0.548, P < .001), and patients with high CCL2 expression presented shorter progression-free survival than those with low CCL2 expression (P < .05). We conclude that CCL2 secreted by TAM activates PI3K/Akt/mTOR signaling and promotes an endocrine resistance feedback loop in the TME, suggesting that CCL2 and TAM may be novel therapeutic targets for patients with endocrineresistant breast cancer.

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Section: Discussionmentioning

confidence: 99%

Tumor‐associated macrophages secrete CC‐chemokine ligand 2 and induce tamoxifen resistance by activating PI3K/Akt/mTOR in breast cancer

et al. 2019

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“…Mantovani et al (20) showed that tumor-associated inflammation is characterized by the swelling of inflammatory cells and the production and release of inflammatory factors in tumor tissues. Inflammatory cells and immune cells, such as neutrophils, lymphocytes, and monocytes, in the peripheral blood of patients with tumor-associated inflammation are considered to be important factors leading to tumor development, invasion and metastasis (21)(22)(23)(24). Existing studies have shown that the NLR and LMR play important roles in determining the prognosis of cancer patients (25-27).…”

Section: Discussionmentioning

confidence: 99%

Value of the preoperative prognostic nutritional index for the evaluation of patient prognosis after radical gastrectomy

et al. 2020

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Preoperative prognostic nutritional index (PNI) has been widely used for the clinical evaluation of patients with cancer. The present study assessed the prognostic value of preoperative PNI in patients after gastric cancer (GC) radical surgery. The clinical case and follow-up data of 170 patients undergoing GC radical surgery were retrospectively analyzed. The receiver operating characteristic (ROC) curve was used to compare the predictive ability of each inflammatory index: The PNI, neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR). The correlation between the preoperative PNI and overall survival (OS) was also analyzed via Kaplan-Meier (K-M) curves and multivariate Cox regression analyses. The results revealed that the optimal PNI cutoff was 46.030. According to this cutoff value, the whole sample was divided into PNI <46.030 (low PNI group) and PNI ≥46.030 (high PNI group). These groups were comprised of 102 and 68 cases, respectively. The area under the curve value of the PNI was 0.725, which was greater than that of traditional inflammatory indices, including the NLR and LMR. K-M survival analysis revealed that the 5 year survival rate of patients in the low PNI group was significantly lower than that of patients in the high PNI group (P<0.01). Univariate analysis and Cox multiple regression model analysis demonstrated that the T stage, N stage, pathological grade and PNI were independent risk factors for the 5 year survival rate after radical gastrectomy (P<0.05). In conclusion, the preoperative PNI is an independent risk factor for 5 year survival after radical gastrectomy and has clinical value for the prognostic evaluation of patients with GC.

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“…More and more evidences showed that neutrophils played an important role in tumor tissue infiltration to promoting the growth, invasion, angiogenesis and metastasis of various types of cancer [19,20]. In addition, studies showed that exosomes as a novel mechanism of intercellular communication, could lead to the exchange of genetic information and reprogramming of recipient cells and transport various biomolecules, such as proteins, messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) [21,22]. Recent studies showed that exosomes play multiple roles in promoting tumor growth, metastasis and drug resistance.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA expression profile in the N2 phenotype neutrophils of colorectal cancer and screen of putative key mircRNAs

Wang

Yang

Huang

et al. 2020

Preprint

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Objective: Colorectal cancer (CRC) is one of the most common malignant tumors in the digestive tract, which accounts for 10% of all the malignant tumors in the world. The aim of this study was to identify key genes and miRNAs in CRC diagnosis, prognosis, and therapy and to further explore the potential molecular mechanisms of CRC.Methods: The infiltration and metastasis of neutrophils in Primary colorectal cancer tissue and Paracancerous tissue were observed by immunohistochemical staining. After inducing N2 neutrophils with TGF-β1 in vitro, exosomes were extracted and sequenced, and then the expression differences of microRNAs were screened by using Agilent microRNA microarrays. The data were imported to the Web CARMA for differential expression analysis. The GO and KEGG enrichment analysis were performed using DIANA-MirPath v3.0 using Targetscan database. And the corresponding targets were imported into Gephi for network analysis. The expression level of differentially expressed microRNA using quantitative Realtime polymerase chain reaction (RT-PCR) was validated.Results: A total of 2 miRNAs were found to be associated with N2 neutrophils, in which the expression of hsa-miR-4780 was upregulated and the expression of hsa-miR-3938 was downregulated in N2 neutrophils, compared with the neutrophils. In addition, the results of miRNA-targets networks showed that the hsa-mir-3938 and hsa-mir-4780 could regulate TUSC1 and ZNF197. The expression level of hsa-miR-4780 and hsa-miR-3938 were validated in accordance with the results of RT-PCR.Conclusion: The hsa-mir-3938 and hsa-mir-4780 were differentially expressed between N2 neutrophils and neutrophils. Moreover, the regulation of TUSC1 and ZNF197 by these DEmiRNA established the theoretical basis for the mechanism of N2 type neutrophils regulating the invasion and metastasis of CRC cells, and provided the potential biomarker for prognosis for clinical treatment of CRC

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Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration

Cited by 243 publications

References 56 publications

Tumor‐associated macrophages secrete CC‐chemokine ligand 2 and induce tamoxifen resistance by activating PI3K/Akt/mTOR in breast cancer

Tumor‐associated macrophages secrete CC‐chemokine ligand 2 and induce tamoxifen resistance by activating PI3K/Akt/mTOR in breast cancer

Value of the preoperative prognostic nutritional index for the evaluation of patient prognosis after radical gastrectomy

MicroRNA expression profile in the N2 phenotype neutrophils of colorectal cancer and screen of putative key mircRNAs

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