Interfering with CCL5/CCR5 at the Tumor-Stroma Interface

Bronte, Vincenzo; Bria, Emilio

doi:10.1016/j.ccell.2016.03.019

Cited by 18 publications

(12 citation statements)

References 11 publications

(21 reference statements)

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“…There are reports shown that fibroblasts involve in the cross-talk of cancer cells and fibroblasts by secreting CCL2 [30–32], CCL5 [33], CXCL1 [34], CXCL6 [35], CXCL12 [36], IL6 [37], CXCL16 [38] and others [23–31]. In the study, we identified that CCL11 and CXCL14 were the target genes of miR-29b in fibroblasts.…”

Section: Discussionmentioning

confidence: 79%

Down-regulation of miR-29b in carcinoma associated fibroblasts promotes cell growth and metastasis of breast cancer

et al. 2017

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Carcinoma associated fibroblasts (CAFs) play important roles in breast cancer development and progression. Recent studies show that microRNAs (miRNAs) are the main regulators in CAFs. MiR-29b is one of the significant down-regulated miRNAs in CAFs from the miRNA screening. The role of miR-29b in the interaction between CAFs and breast cancer is still unclear. In the present study, we investigated the effects of CAFs on breast cancer cell proliferation and metastasis regulated by miR-29b. We found that fibroblasts activated by co-cultured breast cancer cells produced higher levels of some chemokines like CCL11, CXCL14, which accelerated breast cancer cell growth and induced drug resistance and metastasis. Increased miR-29b expression in activated fibroblasts could suppress the activating p38-STAT1 signal pathway in breast cancer cells. We also found that the expression of CCL11 and CXCL14 could be regulated by miR-29b in CAFs. Our results illustrate that down-regulation of miR-29b in CAFs plays an important role in tumor stroma by activating p38-STAT1 in breast cancer cells. The study indicates that cancer cells and fibroblasts interaction promotes breast cancer cell growth, drug resistance, migration and invasion due to the lack of miR-29b expression in CAFs.

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Section: Discussionmentioning

confidence: 79%

Down-regulation of miR-29b in carcinoma associated fibroblasts promotes cell growth and metastasis of breast cancer

et al. 2017

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“…The pro-tumorigenic function of CCR5 is primarily mediated by it ligand CCL5, which promotes proliferation of CCR5-positive tumor cells, recruits immunosuppressive T-regulatory cells and favors metastasis (39). Hence, the CCL5/CCR5 axis has become a potential target for development of novel anticancer therapy (40,41). Arthrosclerosis is increasingly recognized to be a chronic inflammatory disease that involves leukocytes, such as monocytes/macrophages and T cells (42).…”

Section: Discussionmentioning

confidence: 99%

C-C chemokine receptor 5 signaling contributes to cardiac remodeling and dysfunction under pressure overload

Wang

Yue

et al. 2020

Mol Med Rep

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Aortic stenosis (AS) leads to chronic pressure overload, cardiac remodeling and eventually heart failure. Chemokines and their receptors have been implicated in pressure overload-induced cardiac remodeling and dysfunction. In the present study, the role of C-C chemokine receptor 5 (CCR5) in pressure overload-induced cardiac remodeling and dysfunction was investigated in mice subjected to transverse aortic constriction (TAC). Cardiac levels of CCR5 and C-C motif chemokine ligands (CCLs)3, 4 and 5 were determined by western blotting and reverse transcription-quantitative PCR, respectively. Cardiac functional parameters were evaluated by echocardiographic and hemodynamic measurements. Myocardial fibrosis was assessed by Masson's trichrome staining and α-smooth muscle actin immunostaining. Myocardial hypertrophy and inflammatory cell infiltration were evaluated by hematoxylin and eosin staining. Angiotensin II (Ang II)-induced hypertrophy of H9c2 cardiomyocytes was assessed by F-actin immunostaining. ERK1/2 and P38 phosphorylation was examined by western blotting. TAC mice exhibited higher myocardial CCL3, CCL4, CCL5 and CCR5 levels compared with sham mice. Compared with sham mice, TAC mice also exhibited impaired cardiac function along with myocardial hypertrophy, fibrosis and inflammatory cell infiltration. TAC-induced cardiac remodeling and dysfunction were effectively ameliorated by administration of anti-CCR5 but not by IgG control antibody. Mechanistically, increased ERK1/2 and P38 phosphorylation was detected in TAC hearts and Ang II-stimulated H9c2 cardiomyocytes. Treatment with anti-CCR5 antibody decreased ERK1/2 and P38 phosphorylation and attenuated Ang II-induced H9c2 cell hypertrophy. CCR5 inhibition protected against pressure overload-induced cardiac abnormality. The findings of the present study indicate that ERK1/2 and P38 signaling pathways may be involved in the cardioprotective effects of CCR5 inhibition.

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“…The CCL5/CCR5 axis is a potential therapeutic target in different cancer types. Since several studies have demonstrated its involvement in GC progression [ 48 , 101 , 106 , 110 ], counteracting the pro-tumorigenic effects of the CCL5/CCR5 axis with CCR5-antagonists, such as MVC [ 53 , 111 ], or alternatively, with drugs that are capable to of decreasing CCL5 secretion [ 69 ] may be a new therapeutic options for GC treatment.…”

Section: Possible Clinical Applications Of Mvc In Gcmentioning

confidence: 99%

Inhibition of the CCL5/CCR5 Axis against the Progression of Gastric Cancer

Aldinucci

Casagrande

2018

IJMS

109

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Despite the progress made in molecular and clinical research, patients with advanced-stage gastric cancer (GC) have a bad prognosis and very low survival rates. Furthermore, it is challenging to find the complex molecular mechanisms that are involved in the development of GC, its progression, and its resistance to therapy. The interactions of chemokines, also known as chemotactic cytokines, with their receptors regulate immune and inflammatory responses. However, updated research demonstrates that cancer cells subvert the normal chemokine role, transforming them into fundamental constituents of the tumor microenvironment (TME) with tumor-promoting effects. C-C chemokine ligand 5 (CCL5) is a chemotactic cytokine, and its expression and secretion are regulated in T cells. C-C chemokine receptor type 5 (CCR5) is expressed in T cells, macrophages, other leukocytes, and certain types of cancer cells. The interaction between CCL5 and CCR5 plays an active role in recruiting leukocytes into target sites. This review summarizes recent information on the role of the CCL5 chemokine and its receptor CCR5 in GC cell proliferation, metastasis formation, and in the building of an immunosuppressive TME. Moreover, it highlights the development of new therapeutic strategies to inhibit the CCL5/CCR5 axis in different ways and their possible clinical relevance in the treatment of GC.

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Interfering with CCL5/CCR5 at the Tumor-Stroma Interface

Cited by 18 publications

References 11 publications

Down-regulation of miR-29b in carcinoma associated fibroblasts promotes cell growth and metastasis of breast cancer

Down-regulation of miR-29b in carcinoma associated fibroblasts promotes cell growth and metastasis of breast cancer

C-C chemokine receptor 5 signaling contributes to cardiac remodeling and dysfunction under pressure overload

Inhibition of the CCL5/CCR5 Axis against the Progression of Gastric Cancer

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