Role of CXC chemokine receptor type 7 in carcinogenesis and lymph node metastasis of colon cancer

Wang, Hong Xian; Lin, Tongyu; Qi, Kai; Zhang, Hao Yun; Feng, Duo; Wei, Wen Jun; Kong, Heng; Chen, Tian Wen; Lin, Qiu; Chen, Dao Jin

doi:10.3892/mco.2015.643

Cited by 10 publications

(7 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well known that CXCR4 and its ligand CXCL12 play a significant role in tumorigenesis and metastasis of various tumors 4 . Similarly, high expression of CXCR7 has been confirmed in various types of tumors as well and is involved in tumorigenesis, metastasis, and drug resistance 5 - 7 . CXCR7 has been identified as a novel receptor for CXCL12 with higher affinity of binding CXCL12 than CXCR4 in recent years 8 .…”

Section: Introductionmentioning

confidence: 95%

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

Zhao¹,

Zhang²,

Qin³

et al. 2018

J. Cancer

View full text Add to dashboard Cite

Background: Accumulating evidence indicated that the CXC chemokine receptor (CXCR) 7 (CXCR7) was overexpressed in a variety of tumors. However, the value of the CXCR7 expression in predicting prognosis in solid tumors remains controversial. Therefore, we performed this meta-analysis to evaluate the correlation between CXCR7 expression and lymph node metastasis (LNM), tumor pathological grade and survival, including overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS).Methods: Eligible studies were searched in PubMed, Web of Science, and PMC up to April 2018. A total of 27 studies were included in this meta-analysis. Odds ratio (OR), hazard ratio (HR) and 95 % confidence intervals (CI) were used as effect measures.Results: The meta-analysis showed that high expression of CXCR7 predicted a high risk of LNM (pooled OR = 2.22, 95%CI: 1.41-3.50), high tumor grade (pooled OR = 1.94, 95%CI: 1.20-3.13), poor OS (pooled HR = 1.66, 95%CI: 1.30-2.03), and poor DFS/RFS (pooled HR = 1.82, 95%CI: 1.21-2.43). Subgroup analysis showed that CXCR7 expression had a positive correlation with LNM in pan-adenocarcinoma subgroup (pooled OR = 3.73, 95%CI: 2.21-6.30), while no correlation was found in pan-squamous cancer subgroup (pooled OR = 1.29, 95%CI: 0.56-2.96). Subgroup analysis of tumor grade revealed that high expression of CXCR7 predicted high tumor grade both in pan-squamous cancer and pan-adenocarcinoma (pooled OR = 3.58, 95%CI: 1.39-9.22, pooled OR = 2.25, 95%CI: 1.20-4.20). As in OS group, we divided the data based on analysis method and it turned out that overexpressed CXCR7 predicted worse OS both in multivariate analysis (pooled HR =1.57, 95%CI: 1.12-2.01) and univariate analysis subgroup (pooled HR =1.86, 95%CI: 1.23-2.49).Conclusions: Our meta-analysis revealed that high expression of CXCR7 predicted unfavorable prognosis and may serve as potential targets of cancer therapy.

show abstract

Section: Introductionmentioning

confidence: 95%

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

Zhao¹,

Zhang²,

Qin³

et al. 2018

J. Cancer

View full text Add to dashboard Cite

show abstract

“…6 It has been reported that CXCR7 is highly expressed in colon cancer. 7 More recently, numerous studies confirmed that CXCR7 is also expressed in other types of cancer (eg, pancreatic, thyroid, prostate, breast, esophageal, hepatocellular carcinoma, bladder), promoting tumor growth and metastasis. [8][9][10][11][12][13][14] Neovascularization is an essential step for tumor growth, invasion, and metastasis.…”

Section: Introductionmentioning

confidence: 99%

“…Chemokine receptor 7 (CXCR7)—formerly known as RDC1—is the second receptor for C‐X‐C motif chemokine 12 (CXCL12)/stromal cell‐derived factor 1 (SDF‐1), with a 10‐fold higher binding capacity than CXCR4 . It has been reported that CXCR7 is highly expressed in colon cancer . More recently, numerous studies confirmed that CXCR7 is also expressed in other types of cancer (eg, pancreatic, thyroid, prostate, breast, esophageal, hepatocellular carcinoma, bladder), promoting tumor growth and metastasis .…”

Section: Introductionmentioning

confidence: 99%

Chemokine receptor 7 targets the vascular endothelial growth factor via the AKT/ERK pathway to regulate angiogenesis in colon cancer

Wang

et al. 2019

Cancer Medicine

View full text Add to dashboard Cite

Background Studies have shown that CXCR7 is expressed in many tumors. The aim of the present study was to investigate the function of CXCR7 in colon cancer. Although evidence indicates that CXCR7 promotes angiogenesis in colon cancer, the mechanism involved in this process remains unclear. Methods The expression of CXCR7 in colon cancer was evaluated by quantitative reverse‐transcription polymerase chain reaction and western blotting. After transfection, cell proliferation, migration, and lumen formation were measured in vitro. Immunohistochemistry and western blotting were used to identify the functional target of CXCR7 in vivo and in vitro. Results In this study, CXCR7 was differentially expressed in four colon cancer cell lines. The proliferation and migration experiments showed that overexpression of CXCR7 enhanced cell growth and migration. Moreover, the tube formation assays showed that co‐culture of colon cancer cells overexpressing CXCR7 with human umbilical vein endothelial cells significantly promoted tube formation in the latter cells. Conversely, the stable knockdown of CXCR7 significantly reduced this malignant activity. In addition, we found that CXCR7 activates the AKT and ERK pathways in colon cancer cells. The phosphorylation of AKT and ERK, as well as the expression of the vascular endothelial growth factor, can be inhibited using the LY294002 and U0126 inhibitors. Furthermore, the angiogenic ability of CXCR7‐induced colon cancer cells was eliminated. Conclusion Expression of CXCR7 contributes to colon cancer growth and angiogenesis, by activating the AKT and ERK pathways. CXCR7 provides a potential therapeutic target against colon cancer.

show abstract

“…The expression level of CXCR7 in lung tissues is twelve times higher than in liver tissue [ 93 , 103 ]. Increased expression of CXCR7 was also reported in CRC with lymph node metastasis and considered a good predictor of lymph node metastasis in CRC patients [ 104 ]. The systemic treatment with CXCR7 antagonists reduces tumor expansion in lungs of experimental mice inoculated with HT-29 or C26 cancer cells [ 103 ].…”

Section: Signaling In Crc Growth Invasion and Metastasismentioning

confidence: 99%

CXCL12-CXCR4/CXCR7 Axis in Colorectal Cancer: Therapeutic Target in Preclinical and Clinical Studies

Khare

Bissonnette

Khare

2021

IJMS

View full text Add to dashboard Cite

Chemokines are chemotactic cytokines that promote cancer growth, metastasis, and regulate resistance to chemotherapy. Stromal cell-derived factor 1 (SDF1) also known as C-X-C motif chemokine 12 (CXCL12), a prognostic factor, is an extracellular homeostatic chemokine that is the natural ligand for chemokine receptors C-X-C chemokine receptor type 4 (CXCR4), also known as fusin or cluster of differentiation 184 (CD184) and chemokine receptor type 7 (CXCR7). CXCR4 is the most widely expressed rhodopsin-like G protein coupled chemokine receptor (GPCR). The CXCL12–CXCR4 axis is involved in tumor growth, invasion, angiogenesis, and metastasis in colorectal cancer (CRC). CXCR7, recently termed as atypical chemokine receptor 3 (ACKR3), is amongst the G protein coupled cell surface receptor family that is also commonly expressed in a large variety of cancer cells. CXCR7, like CXCR4, regulates immunity, angiogenesis, stem cell trafficking, cell growth and organ-specific metastases. CXCR4 and CXCR7 are expressed individually or together, depending on the tumor type. When expressed together, CXCR4 and CXCR7 can form homo- or hetero-dimers. Homo- and hetero-dimerization of CXCL12 and its receptors CXCR4 and CXCR7 alter their signaling activity. Only few drugs have been approved for clinical use targeting CXCL12-CXCR4/CXCR7 axis. Several CXCR4 inhibitors are in clinical trials for solid tumor treatment with limited success whereas CXCR7-specific inhibitors are still in preclinical studies for CRC. This review focuses on current knowledge of chemokine CXCL12 and its receptors CXCR4 and CXCR7, with emphasis on targeting the CXCL12–CXCR4/CXCR7 axis as a treatment strategy for CRC.

show abstract

Role of CXC chemokine receptor type 7 in carcinogenesis and lymph node metastasis of colon cancer

Cited by 10 publications

References 13 publications

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

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

Chemokine receptor 7 targets the vascular endothelial growth factor via the AKT/ERK pathway to regulate angiogenesis in colon cancer

CXCL12-CXCR4/CXCR7 Axis in Colorectal Cancer: Therapeutic Target in Preclinical and Clinical Studies

Contact Info

Product

Resources

About