CXCR4 signaling regulates metastatic onset by controlling neutrophil motility and response to malignant cells

Annemarie Meijer and Torraca, V. 2019. CXCR4 signaling regulates metastatic onset by controlling neutrophil motility and response to malignant cells. Scientific Reports. 9 2399. https://doi.org/10.1038/s41598-019-38643-2

TitleCXCR4 signaling regulates metastatic onset by controlling neutrophil motility and response to malignant cells
TypeJournal article
AuthorsAnnemarie Meijer and Torraca, V.
Abstract

Developing tumors interact with the surrounding microenvironment. Myeloid cells exert both anti- and pro-tumor functions and chemokines are known to drive immune cell migration towards cancer cells. It is documented that CXCR4 signaling supports tumor metastasis formation in tissues where CXCL12, its cognate ligand, is abundant. On the other hand, the role of the neutrophilic CXCR4 signaling in driving cancer invasion and metastasis formation is poorly understood. Here, we use the zebrafish xenotransplantation model to study the role of CXCR4 signaling in driving the interaction between invasive human tumor cells and host neutrophils, supporting early metastasis formation. We found that zebrafish cxcr4 (cxcr4b) is highly expressed in neutrophils and experimental micrometastases fail to form in mutant larvae lacking a functional Cxcr4b. We demonstrated that Cxcr4b controls neutrophil number and motility and showed that Cxcr4b transcriptomic signature relates to motility and adhesion regulation in neutrophils in tumor-naïve larvae. Finally, Cxcr4b deficient neutrophils failed to interact with cancer cells initiating early metastatic events. In conclusion, we propose that CXCR4 signaling supports the interaction between tumor cells and host neutrophils in developing tumor metastases. Therefore, targeting CXCR4 on tumor cells and neutrophils could serve as a double bladed razor to limit cancer progression.

Article number2399
JournalScientific Reports
Journal citation9
Year2019
PublisherNature Publishing Group
Publisher's version
License
CC BY 4.0
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.1038/s41598-019-38643-2
Publication dates
Published20 Feb 2019

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