PUBLICATION
CXCR4 signaling regulates metastatic onset by controlling neutrophil motility and response to malignant cells
- Authors
- Tulotta, C., Stefanescu, C., Chen, Q., Torraca, V., Meijer, A.H., Snaar-Jagalska, B.E.
- ID
- ZDB-PUB-190223-1
- Date
- 2019
- Source
- Scientific Reports 9: 2399 (Journal)
- Registered Authors
- Meijer, Annemarie H., Snaar-Jagalska, Ewa B.
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Cell Movement/genetics
- Chemokine CXCL12/genetics*
- Disease Models, Animal
- Gene Expression Regulation, Neoplastic
- Heterografts
- Humans
- Larva/genetics
- Mice
- Myeloid Cells/metabolism
- Myeloid Cells/pathology
- Neoplasm Metastasis
- Neoplasms/genetics*
- Neoplasms/pathology
- Neutrophils/metabolism
- Neutrophils/pathology
- Receptors, CXCR4/genetics*
- Transplantation, Heterologous
- Tumor Microenvironment/genetics
- Zebrafish/genetics
- Zebrafish Proteins/genetics*
- PubMed
- 30787324 Full text @ Sci. Rep.
Citation
Tulotta, C., Stefanescu, C., Chen, Q., Torraca, V., Meijer, A.H., Snaar-Jagalska, B.E. (2019) CXCR4 signaling regulates metastatic onset by controlling neutrophil motility and response to malignant cells. Scientific Reports. 9:2399.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping