Tissue factor pathway inhibitor gene transfer prevents vascular smooth muscle cell proliferation by interfering with the MCP-3/CCR2 pathway

Fu, Yu; Ma, Dandan; Liu, Yue; Li, Hui; Chi, Jinyu; Liu, Wenxiu; Lin, Fang-Tsyr; Hu, Jing; Zhang, Xiaohui; Zhu, Minling; Zhao, Yanxin; Yin, Xinhua

doi:10.1038/labinvest.2015.106

Cited by 13 publications

(5 citation statements)

References 40 publications

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“…Recent studies have revealed that CCL7 could directly induce cell proliferation in vitro in coronary artery smooth muscle cells and in vascular smooth muscle cells [33, 34]. In this study, we also found that CCL7 enhanced proliferation of colon cancer cells.…”

Section: Discussionsupporting

confidence: 80%

Crosstalk between CCL7 and CCR3 promotes metastasis of colon cancer cells via ERK-JNK signaling pathways

et al. 2016

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Chemokine ligand 7 (CCL7) enhances cancer progression and metastasis via epithelial-mesenchymal transition (EMT). However, little is known about the molecular mechanism of CCL7-induced EMT signaling cascade in colon cancer. Thus, the objective of this study was to investigate CCL7-induced EMT signaling pathway and its role in the progression and metastasis of colon cancer. To demonstrate the effect of CCL7 on EMT induction, HCT116 and HT29 cells overexpressing CCL7 were generated. CCL7-induced EMT and its downstream signaling pathway were evaluated by both in vitro and in vivo experiments. In in vitro studies, CCL7 was found to interplay with CC chemokine receptor 3 (CCR3), resulting in enhanced cellular proliferation, invasion, and migration via ERK and JNK signaling pathway. To validate these findings, we established ectopic and orthotopic mouse models injected with CCL7-overexpressed cells. In ectopic mouse models, we observed that CCL7-overexpressed cells grew significantly faster than control cells. In orthotopic mouse models, we found that liver and lung metastasis developed only in mice injected with CCL7-overexpressed cells. This study is the first one focusing on the EMT cascade via CCL7-CCR3-ERK-JNK signaling axis in colon cancer. Our novel findings will improve our understanding on the mechanism of metastatic process and provide potential therapeutic strategies for preventing metastasis in colon cancer.

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Section: Discussionsupporting

confidence: 80%

Crosstalk between CCL7 and CCR3 promotes metastasis of colon cancer cells via ERK-JNK signaling pathways

et al. 2016

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“…Previous studies have reported that CCL7 can combine with CCR2 to activate the STAT3 signal pathway and thus promote tumor cell metastasis 22 – 24 . We examined whether Mo-MDSCs secreted CCL7 binds to the CCR2 receptor of dormant HT29 cells.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of CCL7 derived from Mo-MDSCs prevents metastatic progression from latency in colorectal cancer

et al. 2021

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In colorectal cancer (CRC), overt metastases often appear after years of latency. But the signals that cause micro-metastatic cells to remain indolent, thereby enabling them to survive for extended periods of time, are unclear. Immunofluorescence and co-immunoprecipitation assays were used to explore the co-localization of CCL7 and CCR2. Immunohistochemical (IHC) assays were employed to detect the characters of metastatic HT29 cells in mice liver. Flow cytometry assays were performed to detect the immune cells. Bruberin vivo MS FX Pro Imager was used to observe the liver metastasis of CRC in mice. Quantitative real-time PCR (qRT-PCR) and western blot were employed to detect the expressions of related proteins. Trace RNA sequencing was employed to identify differentially expressed genes in MDSCs from liver micro-M and macro-M of CRC in mice. Here, we firstly constructed the vitro dormant cell models and metastatic dormant animal models of colorectal cancer. Then we found that myeloid-derived suppressor cells (MDSCs) were increased significantly from liver micro-metastases to macro-metastases of CRC in mice. Moreover, monocytic MDSCs (Mo-MDSC) significantly promoted the dormant activation of micro-metastatic cells compared to polymorphonuclear MDSCs (PMN-MDSC). Mechanistically, CCL7 secreted by Mo-MDSCs bound with membrane protein CCR2 of micro-metastatic cells and then stimulated the JAK/STAT3 pathway to activate the dormant cells. Low-dose administration of CCL7 and MDSCs inhibitors in vivo could significantly maintain the CRC metastatic cells dormant status for a long time to reduce metastasis or recurrence after radical operation. Clinically, the level of CCL7 in blood was positively related to the number of Mo-MDSCs in CCR patients, and highly linked with the short-time recurrence and distant metastasis. CCL7 secreted by Mo-MDSCs plays an important role in initiating the outgrowth of metastatic latent CRC cells. Inhibition of CCL7 might provide a potential therapeutic strategy for the prevention of metastasis recurrence.

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“…SDF-1α can activate the AKT pathway. 15 We found that SiNPs induced p-AKT (ser473) and p-GSK-3β (ser9) expression in BEAS-2B cells and tumor tissue. Neutralizing SDF-1α with a specific antibody resulted in lower p-GSK-3β (ser9) expression compared with GSK-3β expression and lower p-AKT-ser473 expression compared with AKT expression (Figure 5a and b).…”

Section: Resultsmentioning

confidence: 77%

Spherical silica nanoparticles promote malignant transformation of BEAS-2B cells by stromal cell-derived factor-1α (SDF-1α)

Guo

You

et al. 2019

J Int Med Res

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Objective This study aimed to examine the role of spherical silica nanoparticles (SiNPs) on human bronchial epithelial (BEAS-2B) cells through inflammation. Methods Human mononuclear (THP-1) cells and BEAS-2B cells were co-cultured in transwell chambers and treated with 800 mmol/L benzo[ a]pyrene-7, 8-dihydrodiol-9, 10-epoxide (BPDE) and 12.5 µg/mL SiNPs for 24 hours. For controls, cells were treated with BPDE alone. Subcutaneous tumorigenicity and epithelial-mesenchymal transition (EMT) of BEAS-2B cells were measured. The cells were blocked with a stromal cell-derived factor-1α (SDF-1α)-specific antibody. EMT was analyzed in cells treated with 800 mmol/L BPDE and 12.5 µg/mL SiNPs relative to matched control cells and xenografts in vivo. Serum SDF-1α levels were measured in 23 patients with lung adenocarcinoma in Xuanwei, in 25 with lung adenocarcinoma outside Xuanwei, and in 22 with benign pulmonary lesions in Xuanwei. Results SiNPs significantly promoted tumorigenesis and EMT, induced the release of SDF-1α, and activated AKT (ser473) in BEAS-2B cells. EMT and phosphorylated AKT (ser473) and glycogen synthase kinase-3β levels were decreased when blocked by SDF-1α antibody in BEAS-2B cells. SDF-1α was mainly secreted by THP-1 cells. Conclusion SiNPs combined with BPDE promote EMT of BEAS-2B cells via the AKT pathway by inducing release of SDF-1α from THP-1 cells.

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Tissue factor pathway inhibitor gene transfer prevents vascular smooth muscle cell proliferation by interfering with the MCP-3/CCR2 pathway

Cited by 13 publications

References 40 publications

Crosstalk between CCL7 and CCR3 promotes metastasis of colon cancer cells via ERK-JNK signaling pathways

Crosstalk between CCL7 and CCR3 promotes metastasis of colon cancer cells via ERK-JNK signaling pathways

Inhibition of CCL7 derived from Mo-MDSCs prevents metastatic progression from latency in colorectal cancer

Spherical silica nanoparticles promote malignant transformation of BEAS-2B cells by stromal cell-derived factor-1α (SDF-1α)

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