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Implications of CXCR4/CXCL12 Interaction for Cancer Stem Cell Maintenance and Cancer Progression

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Cancer Stem Cells: Emerging Concepts and Future Perspectives in Translational Oncology

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Abstract

The chemokine receptor type 4 (CXCR4) is known to be involved in immunodeficiency disorders and contributes to different stages of cancer development. The CXCR4 expression level in cancer cells is an adverse prognostic indicator independent from other prognostic factors. Novel findings are pointing out the expression of CXCR4 in the tumor-initiating cancer stem cells (CSCs), which are involved in therapy resistance, relapse, metastasis and poor clinical outcome. CSCs are regulated by signals generated by the tumor microenvironment, but the exact mechanisms are not fully understood. Recent studies provide evidence for an important role of the CXCR4/CXCL12 axis for CSC maintenance, dissemination and metastatic colonization. In addition, this signaling pathway has a crucial contribution in modulation of the tumor microenvironment by inducing neo-angiogenesis and the recruitment of pro-tumorigenic myeloid cells to impede innate and adaptive immune mechanisms of tumor destruction. Moreover, binding of the chemokine ligand CXCL12 to its receptor CXCR4 has a direct effect on cell survival and growth of malignant cells. The correlation of CXCR4 expression with cancer stage and patient outcome makes CXCR4 an important prognostic marker as well as a druggable target with great potential for tumor sensitization to anti-cancer therapies.

Author contributed equally with all other contributors.

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Acknowledgement

The authors indicated no potential conflicts of interest. The authors are supported by the Bundesministerium für Bildung und Forschung (BMBF-03Z1NN11).

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    1. OncoRay-National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Fetscherstrasse 74, 01307, Dresden, Germany

      Claudia Peitzsch, Monica Cojoc, Ina Kurth & Anna Dubrovska

    2. German Cancer Consortium (DKTK) Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany

      Anna Dubrovska

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      Sadegh Babashah

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    Peitzsch, C., Cojoc, M., Kurth, I., Dubrovska, A. (2015). Implications of CXCR4/CXCL12 Interaction for Cancer Stem Cell Maintenance and Cancer Progression. In: Babashah, S. (eds) Cancer Stem Cells: Emerging Concepts and Future Perspectives in Translational Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-21030-8_4

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