Myeloid-Derived Suppressor Cells Recruited by Chemokine (C-C Motif) Ligand 3 Promote the Progression of Breast Cancer via Phosphoinositide 3-Kinase-Protein Kinase B-Mammalian Target of Rapamycin Signaling

Anqi Luo; Min Meng; Guanying Wang; Rui Han; Yujiao Zhang; Xin Jing; Lin Zhao; Shanzhi Gu; Xinhan Zhao

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저자정보: Anqi Luo (Department of Nuclear medicine National Cancer Center/Cancer Hospital Chinese Academy of Medical) Min Meng (Department of Oncology Shandong Provincial Hospital Affiliated with Shandong University Jinan Chi) Guanying Wang (Department of Oncology First Affiliated Hospital of Medical School of Xi'an Jiaotong University Xi) Rui Han (Department of Oncology First Affiliated Hospital of Zhengzhou University Zhengzhou China) Yujiao Zhang (Department of Oncology First Affiliated Hospital of Medical School of Xi'an Jiaotong University Xi) Xin Jing (Department of Oncology First Affiliated Hospital of Medical School of Xi'an Jiaotong University Xi) Lin Zhao (Department of Oncology First Affiliated Hospital of Medical School of Xi'an Jiaotong University Xi) Shanzhi Gu (Department of Forensic Medicine Medical School of Xi'an Jiaotong University Xi'an China) Xinhan Zhao (Department of Oncology First Affiliated Hospital of Medical School of Xi'an Jiaotong University Xi)

저널정보: 한국유방암학회 Journal of Breast Cancer Journal of Breast Cancer Vol.23 No.2

발행연도: 2020.1

수록면: 141 - 161 (21page)

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Purpose: Numerous studies have shown that the frequency of myeloid-derived suppressor cells (MDSCs) is associated with tumor progression, metastasis, and recurrence. Chemokine (C-C motif ) ligand 3 (CCL3) may be secreted by tumor cells and attract MDSCs into the tumor microenvironment. In the present study, we aimed to explore the molecular mechanisms whereby CCL3 is involved in the interaction of breast cancer cells and MDSCs. Methods: The expression of CCL3 and its receptors was investigated using real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The cell counting Kit-8, wound healing, and transwell assays were performed to study cell growth, migration, and invasion. Cell cycling, apoptosis, and the frequency of MDSCs were investigated through flow cytometry. Transwell assays were used for co-culture and chemotaxis detection. Markers of the epithelial-mesenchymal transition (EMT) were determined with western blotting. The role of CCL3 in vivo was studied via tumor xenograft experiments. Results: CCL3 promoted cell proliferation, migration, invasion, and cycling, and inhibited apoptosis of breast cancer cells in vitro. Blocking CCL3 in vivo inhibited tumor growth and metastases. The frequency of MDSCs in patients with breast cancer was higher than that in healthy donors. Additionally, MDSCs might be recruited by CCL3. Co-culture with MDSCs activated the phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin (PI3K-Akt-mTOR) pathway and promoted the EMT in breast cancer cells, and their proliferation, migration, and invasion significantly increased. These changes were not observed when breast cancer cells with CCL3 knockdown were co-cultured with MDSCs. Conclusion: CCL3 promoted the growth of breast cancer cells, and MDSCs recruited by CCL3 interacted with these cells and then activated the PI3K-Akt-mTOR pathway, which led to EMT and promoted the migration and invasion of the cells.

#Breast neoplasms #Chemokine CCL3 #Epithelial-mesenchymal transition #Myeloid-derived suppressor cells #Tumor microenvironment

참고문헌 (29)

참고문헌 신청

Rodvold JJ / 2016 / Tumor microenvironment on the move and the Aselli connection / Sci Signal 9:fs13

Gabrilovich DI / 2007 / The terminology issue for myeloid-derived suppressor cells / Cancer Res 67:425~426

Katoh H / 2015 / Myeloid-derived suppressor cells and therapeutic strategies in cancer / Mediators Inflamm 2015:159269

Gabitass RF / 2011 / Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13 / Cancer Immunol Immunother 60:1419~1430

Yaddanapudi K / 2016 / MIF is necessary for late-stage melanoma patient MDSC immune suppression and differentiation / Cancer Immunol Res 4:101~112

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Anqi Luo

소속기관 Department of Nuclear medicine National Cancer Center/Cancer Hospital Chinese Academy of Medical