ArticleBreast cancer research : BCR2014
C-X-C motif chemokine 12/C-X-C chemokine receptor type 7 signaling regulates breast cancer growth and metastasis by modulating the tumor microenvironment.
Article in Breast cancer research : BCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- A meta-analysis of CXCL12 expression for cancer prognosis.British journal of cancer · 2017Pooled it
- Single-cell landscape of intratumoral heterogeneity and GABA-mediated remodeling of the immune microenvironment in breast cancer metastases.Breast cancer research : BCR · 2026Article
- Cytokine Networks in Triple-Negative Breast Cancer: Mechanisms, Therapeutic Targets, and Emerging Strategies.Biomedicines · 2025Review
- Catechin suppresses HNSC via STXBP1 dependent inhibition of macrophage infiltration and CD47 mediated immune evasion.Scientific reports · 2025Article
- Comparative Transcriptomics Study of Curcumin and Conventional Therapies in Translocation, Clear Cell, and Papillary Renal Cell Carcinoma Subtypes.International journal of molecular sciences · 2025Article
- Caveolin-1 knockout mitigates breast cancer metastasis to the lungs via integrin α3 dysregulation in 4T1-induced syngeneic breast cancer model.Cancer gene therapy · 2024Article
- Review
- Curcumin Disrupts a Positive Feedback Loop between ADMSCs and Cancer Cells in the Breast Tumor Microenvironment via the CXCL12/CXCR4 Axis.Pharmaceutics · 2023Article
- Chemokine receptor CXCR7 activates Aurora Kinase A and promotes neuroendocrine prostate cancer growth.The Journal of clinical investigation · 2023Article
- The Significance of CXCL1 and CXCR1 as Potential Biomarkers of Colorectal Cancer.Biomedicines · 2023Article
- Thymoquinone Inhibition of Chemokines in TNF-α-Induced Inflammatory and Metastatic Effects in Triple-Negative Breast Cancer Cells.International journal of molecular sciences · 2023Article
- Review
- A novel prognostic signature of chemokines for survival and immune infiltration in kidney renal clear cell carcinoma.International journal of medical sciences · 2023Article
- CXCL12-CXCR4/CXCR7 Axis in Cancer: from Mechanisms to Clinical Applications.International journal of biological sciences · 2023Review
- The multifaceted roles of matrix metalloproteinases in lung cancer.Frontiers in oncology · 2023Review
- Rethinking the chemokine cascade in brain metastasis: Preventive and therapeutic implications.Seminars in cancer biology · 2022Review
- Comprehensive analysis of CXCR family members in lung adenocarcinoma with prognostic values.BMC pulmonary medicine · 2022Article
- Macrophages Are a Double-Edged Sword: Molecular Crosstalk between Tumor-Associated Macrophages and Cancer Stem Cells.Biomolecules · 2022Review
- Review
- Therapeutic Approaches Targeting Proteins in Tumor-Associated Macrophages and Their Applications in Cancers.Biomolecules · 2022Review
12 more citing papers are in PubMed but not listed here.
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7 authors at 2 institutions in 1 country.
Funding
Abstract
introductionAlthough C-X-C motif chemokine 12 (CXCL12) has been shown to bind to C-X-C chemokine receptor type 7 (CXCR7), the exact molecular mechanism regulations by CXCL12/CXCR7 axis in breast tumor growth and metastasis are not well understood. CXCR7 expression has been shown to be upregulated during pathological processes such as inflammation and cancer.
methodsBreast cancer cell lines were genetically silenced or pharmacologically inhibited for CXCR7 and/or its downstream target signal transducer and activator of transcription 3 (STAT3). 4T1 or 4T1 downregulated for CXCR7 and 4T1.2 breast cancer cell lines were injected in mammary gland of BALB/c mice to form tumors, and the molecular pathways regulating tumor growth and metastasis were assessed.
resultsIn this study, we observed that CXCL12 enhances CXCR7-mediated breast cancer migration. Furthermore, genetic silencing or pharmacologic inhibition of CXCR7 reduced breast tumor growth and metastasis. Further elucidation of mechanisms revealed that CXCR7 mediates tumor growth and metastasis by activating proinflammatory STAT3 signaling and angiogenic markers. Furthermore, enhanced breast tumorigenicity and invasiveness were associated with macrophage infiltration. CXCR7 recruits tumor-promoting macrophages (M2) to the tumor site through regulation of the macrophage colony-stimulating factor (M-CSF)/macrophage colony-stimulating factor receptor (MCSF-R) signaling pathway. In addition, CXCR7 regulated breast cancer metastasis by enhancing expression of metalloproteinases (MMP-9, MMP-2) and vascular cell-adhesion molecule-1 (VCAM-1). We also observed that CXCR7 is highly expressed in invasive ductal carcinoma (IDC) and metastatic breast tissue in human patient samples. In addition, high CXCR7 expression in tumors correlates with worse prognosis for both overall survival and lung metastasis-free survival in IDC patients.
conclusionThese observations reveal that CXCR7 enhances breast cancer growth and metastasis via a novel pathway by modulating the tumor microenvironment. These findings identify CXCR7-mediated STAT3 activation and modulation of the tumor microenvironment as novel regulation of breast cancer growth and metastasis. These studies indicate that new strategies using CXCR7 inhibitors could be developed for antimetastatic therapy.
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