Role of CXCR7 as a Common Predictor for Prognosis in Solid Tumors: a Meta-Analysis

Zhao, Qitai; Zhang, Penghua; Qin, Guohui; Ren, Feifei; Yang, Zheng; Qiao, Ying; Sun, Ting; Zhang, Yi

doi:10.7150/jca.25377

Cited by 9 publications

(7 citation statements)

References 47 publications

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“…Decreased CXCR7 expression in zebrafish embryos inhibits blood vessel formation 42 , and its loss in mice causes early postnatal mortality as a result of myocardial degeneration and heart vessel damage 43 . In parallel, CXCR7 is also known to play an integral role in tumor progression by inducing tumor cell proliferation, adhesion, invasion, as well as tube formation in vitro and promotes tumor growth in vivo [44][45][46][47] . Studying the role of CXCR7 in PAH was not in the scope of this study, but will deserve further investigations.…”

Section: Discussionmentioning

confidence: 99%

Neutralization of CXCL12 attenuates established pulmonary hypertension in rats

Bordenave

Thuillet

et al. 2019

Cardiovascular Research

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Aims The progressive accumulation of cells in pulmonary vascular walls is a key pathological feature of pulmonary arterial hypertension (PAH) that results in narrowing of the vessel lumen, but treatments targeting this mechanism are lacking. The C-X-C motif chemokine 12 (CXCL12) appears to be crucial in these processes. We investigated the activity of two CXCL12 neutraligands on experimental pulmonary hypertension (PH), using two complementary animal models. Methods and results Male Wistar rats were injected with monocrotaline (MCT) or were subjected to SU5416 followed by 3-week hypoxia to induce severe PH. After PH establishment, assessed by pulsed-wave Doppler echocardiography, MCT-injected or SU5416 plus chronic hypoxia (SuHx) rats were randomized to receive CXCL12 neutraligands chalcone 4 or LIT-927 (100 mg/kg/day), the C-X-C motif chemokine receptor 4 (CXCR4) antagonist AMD3100 (5 mg/kg/day), or vehicle, for 2 or 3 weeks, respectively. At the end of these treatment periods, echocardiographic and haemodynamic measurements were performed and tissue samples were collected for protein expression and histological analysis. Daily treatment of MCT-injected or SuHx rats with established PH with chalcone 4 or LIT-927 partially reversed established PH, reducing total pulmonary vascular resistance, and remodelling of pulmonary arterioles. Consistent with these observations, we found that neutralization of CXCL12 attenuates right ventricular hypertrophy, pulmonary vascular remodelling, and decreases pulmonary artery smooth muscle cell (PA-SMC) proliferation in lungs of MCT-injected rats and SuHx rats. Importantly, CXCL12 neutralization with either chalcone 4 or LIT-927 inhibited the migration of PA-SMCs and pericytes in vitro with a better efficacy than AMD3100. Finally, we found that CXCL12 neutralization decreases vascular pericyte coverage and macrophage infiltration in lungs of both MCT-injected and SuHx rats. Conclusion We report here a greater beneficial effect of CXCL12 neutralization vs. the conventional CXCR4 blockade with AMD3100 in the MCT and SuHx rat models of severe PH, supporting a role for CXCL12 in the progression of vascular complications in PH and opening to new therapeutic options.

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Section: Discussionmentioning

confidence: 99%

Neutralization of CXCL12 attenuates established pulmonary hypertension in rats

Bordenave

Thuillet

et al. 2019

Cardiovascular Research

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“…Increased expression of CXCR7 has been observed in pancreatic, prostate, liver, ovarian, kidney, colon, breast and lung cancer [ 116 ], and in general there is a positive correlation between CXCR7 expression and tumor malignancy [ 117 ]. In addition, high expression of CXCR7 confers a high risk of developing lymph node metastasis [ 118 ].…”

Section: Cxcl12/cxcr4 and Cxcl12/cxcr7mentioning

confidence: 99%

Role of Chemokines in the Biology of Cholangiocarcinoma

Caligiuri

Pastore

Lori

et al. 2020

Cancers

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Cholangiocarcinoma (CCA), a heterogeneous tumor with poor prognosis, can arise at any level in the biliary tree. It may derive from epithelial cells in the biliary tracts and peribiliary glands and possibly from progenitor cells or even hepatocytes. Several risk factors are responsible for CCA onset, however an inflammatory milieu nearby the biliary tree represents the most common condition favoring CCA development. Chemokines play a key role in driving the immunological response upon liver injury and may sustain tumor initiation and development. Chemokine receptor-dependent pathways influence the interplay among various cellular components, resulting in remodeling of the hepatic microenvironment towards a pro-inflammatory, pro-fibrogenic, pro-angiogenic and pre-neoplastic setting. Moreover, once tumor develops, chemokine signaling may influence its progression. Here we review the role of chemokines in the regulation of CCA development and progression, and the modulation of angiogenesis, metastasis and immune control. The potential role of chemokines and their receptors as possible biomarkers and/or therapeutic targets for hepatobiliary cancer is also discussed.

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“…Its role in tumorigenesis in colorectal cancer is likely through histone demethylation via a CXCR4/CXCR7 heterodimer [53]. Overall, the overexpression of CXCR7 is significantly correlated to lowered overall survival, disease-free survival, recurrence-free survival and progression-free survival [54][55][56]. In solid tumors, high levels of CXCR7 predict a high risk of lymph node metastasis [55].…”

Section: The Role Of Cxcr7 In Cancersmentioning

confidence: 99%

“…Overall, the overexpression of CXCR7 is significantly correlated to lowered overall survival, disease-free survival, recurrence-free survival and progression-free survival [54][55][56]. In solid tumors, high levels of CXCR7 predict a high risk of lymph node metastasis [55]. In gastric cancer, lipopolysaccharide induces the TLR4 (toll-like receptor 4)/MD-2 (myeloid differential protein-2) pathway, which leads to the upregulation of CXCR7, and ultimately tumor growth and metastasis [57].…”

Section: The Role Of Cxcr7 In Cancersmentioning

confidence: 99%

Advances in CXCR7 Modulators

Lounsbury

2020

Pharmaceuticals

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CXC chemokine receptor 7 (CXCR7) is a G-protein-coupled receptor that signals through the β-arrestin pathway. Its ligands include interferon-inducible T cell α chemoattractant (CXCL11) and stromal cell-derived factor-1 (CXCL12). It interacts with CXCR4, and the two are associated with various cancers, as well as other disease states such as coronary artery disease, stroke, inflammation and human immunodeficiency virus (HIV). Antibodies and small interfering RNA (siRNA) have shown the utility of antagonists of CXCR7 in these disease states. Although some small molecules were initially reported as antagonists due to their displayed activity, many function as agonists while still producing the desired pharmacologic effects. A potential reason for this contradiction is that effects may be due to elevated extracellular CXCL12 levels.

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Role of CXCR7 as a Common Predictor for Prognosis in Solid Tumors: a Meta-Analysis

Cited by 9 publications

References 47 publications

Neutralization of CXCL12 attenuates established pulmonary hypertension in rats

Neutralization of CXCL12 attenuates established pulmonary hypertension in rats

Role of Chemokines in the Biology of Cholangiocarcinoma

Advances in CXCR7 Modulators

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