Estrogen promotes progression of hormone-dependent breast cancer through CCL2-CCR2 axis by upregulation of Twist via PI3K/AKT/NF-κB signaling

Han, Rui; Gu, Shanzhi; Zhang, Yujiao; Luo, Anqi; Jing, Xin; Zhao, Lin; Zhao, Xinhan; Zhang, Lingxiao

doi:10.1038/s41598-018-27810-6

Cited by 72 publications

(60 citation statements)

References 50 publications

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“…These results correlated with recent in vitro and in vivo clinical data, where bone marrow-derived macrophage efferocytosis of cancer cells promotes the expression of CCL5, CXCL1, CXCL5, and IL-6 pro-inflammatory cytokines that accelerate tumor progression in the bone microenvironment [7]. The roles of these cytokines have been previously associated with tumor inflammation mechanisms and metastasis in various cancer types [7,[35][36][37][38]. In accordance with this hypothesis, we found that inducing bone marrow macrophage repolarization with IFN-γ towards M1-type resulted in a significant downregulation of Cxcl1, Cxcl4, and Cxcl5 expression in efferocytic macrophages, which was corroborated by the CXCL1 and CXCL5 ELISA results.…”

Section: Discussionsupporting

confidence: 87%

Unique Pro-Inflammatory Response of Macrophages during Apoptotic Cancer Cell Clearance

Mendoza-Reinoso

Baek

Kurutz

et al. 2020

Cells

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The clearance of apoptotic cells by macrophages (efferocytosis) is crucial to maintain normal tissue homeostasis; however, efferocytosis of cancer cells frequently results in inflammation and immunosuppression. Recently, we demonstrated that efferocytosis of apoptotic prostate cancer cells by bone marrow-derived macrophages induced a pro-inflammatory response that accelerated metastatic tumor growth in bone. To evaluate the microenvironmental impact of macrophages and their efferocytic function, we compared peritoneal macrophages (P-MΦ) versus bone marrow-derived macrophages (BM-MΦs) using an efferocytosis in vitro model. The capability to engulf apoptotic prostate cells was similar in BM-MΦs and P-MΦs. Ex vivo analysis of BM-MΦs showed an M2-like phenotype compared with a predominantly M1-like phenotype in P-MΦs. A distinct gene and protein expression profile of pro-inflammatory cytokines was found in BM-MΦs as compared with P-MΦs engulfing apoptotic prostate cancer cells. Importantly, the reprogramming of BM-MΦs toward an M1-like phenotype mitigated their inflammatory cytokine expression profile. In conclusion, BM-MΦs and P-MΦs are both capable of efferocytosing apoptotic prostate cancer cells; however, BM-MΦs exert increased inflammatory cytokine expression that is dependent upon the M2 polarization stage of macrophages. These findings suggest that bone marrow macrophage efferocytosis of apoptotic cancer cells maintains a unique pro-inflammatory microenvironment that may support a fertile niche for cancer growth. Finally, bone marrow macrophage reprogramming towards M1-type by interferon-γ (IFN-γ) induced a significant reduction in the efferocytosis-mediated pro-inflammatory signature.

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Section: Discussionsupporting

confidence: 87%

Unique Pro-Inflammatory Response of Macrophages during Apoptotic Cancer Cell Clearance

Mendoza-Reinoso

Baek

Kurutz

et al. 2020

Cells

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“…In mice that have received the subcutaneous injection of LLC cancer cells, treatment with a CCR2 antagonist (RS504393) inhibits the establishment of lung metastatic foci ( 100 ). A recent study also showed that another CCR2 antagonist (RS102896) can suppress liver metastasis of MCF-7 human breast cancer cells induced by estrogen ( 101 ). Furthermore, in mice that have developed orthotopic tumors by 4T1 mammary tumor cells, treatment with a CCR5 antagonist (maraviroc) reduces metastatic tumor burden in the lung ( 95 ).…”

Section: Therapeutic Potential Of Chemokine Antagonists To Prevent Mamentioning

confidence: 99%

Targeting Macrophage-Recruiting Chemokines as a Novel Therapeutic Strategy to Prevent the Progression of Solid Tumors

2018

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Solid tumors are initiated by genetic mutations in non-hematopoietic cells and progress into invasive malignant tumors. This tumor progression often culminates in metastatic disease that is largely refractory to current therapeutic modalities and thus dramatically reduces survival of tumor patients. As solid tumors account for more than 80% of cancer-related deaths, it is necessary to develop novel therapeutic strategies to treat the diseases. An attractive strategy is to target macrophages in both primary tumors [known as tumor-associated macrophages (TAMs)] and metastatic tumors [called metastasis-associated macrophages (MAMs)]. TAMs and MAMs are abundant in most solid tumors and can promote tumor metastasis. Several studies in various models of solid tumors suggest that the accumulation of TAMs, MAMs, and their progenitor cells is regulated by chemokine ligands released by tumor and stromal cells. Consequently, these macrophage-recruiting chemokines could be potential therapeutic targets to prevent malignant tumor development through disruption of the accumulation of pro-metastatic macrophages. This review will discuss the role of chemokine ligands and their receptors in TAM and MAM accumulation in primary and secondary tumor sites, and finally discuss the therapeutic potential of inhibitors against these macrophage-recruiting chemokines.

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“…NF-κB and STAT3 have been revealed to regulate inflammation and cell adhesion [ 35 ]. In addition, Twist had the function of regulating NF-κB pathway [ 36 ]. In our study, the expression of Twist, NF-κB and STAT3 were detected to evaluate the NF-κB signaling pathway in high glucose-induced HGMCs and HRGECs.…”

Section: Discussionmentioning

confidence: 99%

LncRNA KCNQ1OT1 affects cell proliferation, apoptosis and fibrosis through regulating miR-18b-5p/SORBS2 axis and NF-ĸB pathway in diabetic nephropathy

Ran

Zhu

Zhong

et al. 2020

Diabetol Metab Syndr

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Background It has been reported that long non-coding RNAs (lncRNAs) play vital roles in diabetic nephropathy (DN). Our study aims to research the function of lncRNA KCNQ1OT1 in DN cells and the molecular mechanism. Methods Human glomerular mesangial cells (HGMCs) and human renal glomerular endothelial cells (HRGECs) were cultured in high glucose (30 mM) condition as models of DN cells. KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) and miR-18b-5p levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The mRNA and protein levels of Sorbin and SH3 domain-containing protein 2 (SORBS2), Type IV collagen (Col-4), fibronectin (FN), transcriptional regulatory factor-beta 1 (TGF-β1), Twist, NF-κB and STAT3 were measured by qRT-PCR and western blot. Cell viability was detected by cell counting kit-8 (CCK-8) assay for selecting the proper concentration of glucose treatment. Additionally, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry assay were employed to determine cell proliferation and apoptosis, respectively. The targets of KCNQ1OT1 was predicted by online software and confirmed by dual-luciferase reporter assay. Results KCNQ1OT1 and SORBS2 were elevated in DN. Both knockdown of KCNQ1OT1 and silencing of SORBS2 restrained proliferation and fibrosis and induced apoptosis in DN cells. Besides, Overexpression of SORBS2 restored the KCNQ1OT1 knockdown-mediate effects on proliferation, apoptosis and fibrosis in DN cells. In addition, miR-18b-5p served as a target of KCNQ1OT1 as well as targeted SORBS2. KCNQ1OT1 knockdown repressed NF-ĸB pathway. Conclusion KCNQ1OT1 regulated DN cells proliferation, apoptosis and fibrosis via KCNQ1OT1/miR-18b-5p/SORBS2 axis and NF-ĸB pathway.

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Estrogen promotes progression of hormone-dependent breast cancer through CCL2-CCR2 axis by upregulation of Twist via PI3K/AKT/NF-κB signaling

Cited by 72 publications

References 50 publications

Unique Pro-Inflammatory Response of Macrophages during Apoptotic Cancer Cell Clearance

Unique Pro-Inflammatory Response of Macrophages during Apoptotic Cancer Cell Clearance

Targeting Macrophage-Recruiting Chemokines as a Novel Therapeutic Strategy to Prevent the Progression of Solid Tumors

LncRNA KCNQ1OT1 affects cell proliferation, apoptosis and fibrosis through regulating miR-18b-5p/SORBS2 axis and NF-ĸB pathway in diabetic nephropathy

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