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ORIGINAL RESEARCH
Expression of chemokine receptors CXCR4 and CXCR7 in EpCAM-positive and EpCAM-negative CTCs in breast cancer
1 Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia
2 Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia
Correspondence should be addressed: Evgeniya S. Grigoryeva
per. Kooperativny, 5, Tomsk, 634009, Russia; moc.liamg@se.aveyrogirg
Funding: the study was supported by the Russian Science Foundation (grant No. 23-15-00135).
Author contribution: Grigorieva ES, Savelieva OE, Zavyalova MV — data collection and analysis; Grigorieva ES, Tashireva LA — writing and editing; Perelmuter VM — research supervision; Cherdyntseva NV — project funding.
Compliance with ethical standards: the study was approved by the Local Ethics Committee of Tomsk National Research Medical Center (17 June 2016, the approval No. 8) and complied with the Declaration of Helsinki. All participants gave written informed consent.
- Thomas-Bonafos T, Pierga JY, Bidard FC, Cabel L, Kiavue N, et al. Circulating tumor cells in breast cancer: clinical validity and utility. NPJ Breast Cancer. 2024; 10: 103.
- Ju S, Chen C, Zhang J, Xu L, Zhang X, Li Z, Chen Y, Zhou J, Ji F, Wang L, et al. Detection of circulating tumor cells: opportunities and challenges. Biomark Res. 2022; 10: 58.
- Eslami-S Z, Cortés-Hernández LE, Alix-Panabières C. Epithelial Cell Adhesion Molecule: An Anchor to Isolate Clinically Relevant Circulating Tumor Cells. Cells. 2020; 9: 1836.
- Riethdorf S, Fritsche H, Müller V, Rau T, Schindlbeck C, Rack B, Janni W, Coith C, Beck K, Jänicke F, et al. Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: A validation study of the CellSearch system. Clin Cancer Res. 2007; 13: 920–28.
- Ye F, Zhong X, Qiu Y, Yang L, Wei B, Zhang Z, Bu H. The presence of EpCAM–/CD49f+ cells in breast cancer is associated with a poor clinical outcome. J Breast Cancer. 2015; 18: 242–8.
- Nieto MA, Huang RY, Jackson RA, Thiery JP. Cell. 2016; 166: 21–45.
- Aiello NM, Kang Y. Context-dependent EMT programs in cancer metastasis. J Exp Med. 2019; 216: 1016–26.
- Rueda A, Serna N, Mangues R, Vázquez E, Villaverde A. Targeting the chemokine receptor CXCR4 for cancer therapies. Biomark Res. 2025; 13: 68.
- Chatterjee S, Behnam Azad B, Nimmagadda S. The intricate role of CXCR4 in cancer. Adv Cancer Res. 2014; 124: 31–82.
- Boldajipour B, Mahabaleshwar H, Kardash E, Reichman-Fried M, Blaser H, Minina S, et al. Control of chemokine-guided cell migration by ligand sequestration. Cell. 2008; 132: 463–73.
- Yang Y, Li J, Lei W. CXCL12-CXCR4/CXCR7 Axis in Cancer: from Mechanisms to Clinical Applications. Int J Biol Sci. 2023; 19: 3341–59.
- Wu C, Zhao H, Chen H, Yao Q. CXCR4 in breast cancer: oncogenic role and therapeutic targeting. Drug Des Devel Ther. 2015; 9: 4953–64.
- Pospelova RA. Leukocyte concentration in clinical practice: diagnostic value. M.: Meditsina, 1973.
- Menyailo M, Zainullina V, Khozyainova A, Tashireva L, Zolotareva S, Gerashchenko T, et al. Heterogeneity of Circulating Epithelial Cells in Breast Cancer at Single-Cell Resolution: Identifying Tumor and Hybrid Cells. Adv Biol (Weinh). 2023; 7: e2200206.
- Satija Lab. Seurat: Tools for Single Cell Genomics. GitHub. 2023. Available from: https://github.com/satijalab/seurat.
- McGinnis CS. DoubletFinder: Doublet Detection in Single- Cell RNA Sequencing Data. GitHub. 2023. Available from: https://github.com/chris-mcginnis-ucsf/DoubletFinder.
- Tashireva L, Grigoryeva E, Alifanov V, et al. Spatial Heterogeneity of Integrins and Their Ligands in Primary Breast Tumors. Discov Med. 2023; 35: 910–20.
- Hafemeister C, Satija R. Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression. Genome Biol. 2019; 20: 296.
- Mego M, Cholujova D, Minarik G, Sedlackova T, Gronesova P, Karaba M, et al. CXCR4-SDF-1 interaction potentially mediates trafficking of circulating tumor cells in primary breast cancer. BMC Cancer. 2016; 16: 127T.
- Shi Q, Yang W, Ouyang Y, Zhou S, Xu L, Liu J, et al. CXCR4 promotes tumor stemness maintenance and CDK4/6 inhibitors resistance in ER-positive breast cancer. Breast Cancer Res. 2025; 27: 15.
- Nengroo MA, Maheshwari S, Singh A, Verma A, Arya RK, Chaturvedi P, et al. CXCR4 intracellular protein promotes drug resistance and tumorigenic potential by inversely regulating the expression of Death Receptor 5. Cell Death Dis. 2021; 12: 464.
- Garg P, Jallepalli VR, Verma S. Unravelling the CXCL12/CXCR4 Axis in breast cancer: Insights into metastasis, microenvironment interactions, and therapeutic opportunities. Hum Gene. 2024; 40: 201272.
- Jolly MK, Mani SA, Levine H. Hybrid epithelial/mesenchymal phenotype(s): The 'fittest' for metastasis? Biochim Biophys Acta Rev Cancer. 2018; 1870: 151–7.
- Fabregat I, Malfettone A, Soukupova J. New Insights into the Crossroads between EMT and Stemness in the Context of Cancer. J Clin Med. 2016; 5: 37.
- Ponzetti M, Capulli M, Angelucci A, Delle Monache S, Sica AR, Festuccia C, et al. Non-conventional role of haemoglobin beta in breast malignancy. Br J Cancer. 2017; 117: 994–1006.
- Zhang X, Yang H, Zhang L, Li Y, Ma H. A Pan-Cancer Analysis of the Hemoglobin Subunit Beta (HBB) in Human Tumors. Front Genet. 2022; 13: 880647.
- Chang YT, Tsai WC, Lin WZ, Chen YS, Hou MF, Wu YC, et al. A Novel IGLC2 Gene Linked With Prognosis of Triple-Negative Breast Cancer. Front Oncol. 2022; 11: 759952.
- Tsyganov MM, Ibragimova MK. MALAT1 Long Non-coding RNA and Its Role in Breast Carcinogenesis. Acta Naturae. 2023; 15: 32–41.
- Kim J, Piao HL, Kim BJ, Yao F, Han Z, Wang Y, et al. Long noncoding RNA MALAT1 suppresses breast cancer metastasis. Nat Genet. 2018; 50: 1705–15.
- Qie S, Xiong H, Liu Y, et al. Stanniocalcin 2 governs cancer cell adaptation to nutrient insufficiency through alleviation of oxidative stress. Cell Death Dis. 2024; 15: 567. https://doi.org/10.1038/s41419-024-06961-7.
- Chen S, Zhang X, Basappa B, et al. TFF3 facilitates dormancy of anti-estrogen treated ER+ mammary carcinoma. Commun Med. 2025; 5: 45. https://doi.org/10.1038/s43856-024-00710-9.
- Wang D, Zhao C, Gao L, Wang Y, Gao X, Tang L, et al. NPNT promotes early-stage bone metastases in breast cancer by regulation of the osteogenic niche. J Bone Oncol. 2018; 13: 91– 96. DOI: 10.1016/j.jbo.2018.09.006.