Zebravis tegen kanker: van aquarium tot patiënt

Oratie uitgesproken door prof.dr. B.E. Snaar-Jagalska bij de aanvaarding van het ambt van hoogleraar op het gebied van Cellulaire Tumorbiologie aan de Universiteit Leiden op maandag 11 december 2017Oratie uitgesproken door prof.dr. B.E. Snaar-Jagalska bij de aanvaarding van het ambt van hoogleraar op het gebied van Cellulaire Tumorbiologie aan de Universiteit Leiden op maandag 11 december 2017Animal science

Functions of the MAPK family in vertebrate development

Animal science

Ortho- and ectopic zebrafish xeno-engraftment of ocular melanoma to recapitulate primary tumor and experimental metastasis development

Animal science

The chemokine receptor CXCR4 promotes granuloma formation by sustaining a mycobacteria-induced angiogenesis programme

Animal science

Single-molecule diffusion measurements of H-Ras at the plasma membrane of live cells reveal microdomain localization upon activation

Animal sciencesBiological and Soft Matter Physic

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

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

Embryonic zebrafish xenograft assay of human cancer metastasis

) embryos, however, offer many advantages as a model system for studying the complex, multi-step processes involved during cancer metastasis. This article describes a detailed method for the analysis of human cancer cell invasion and metastasis in zebrafish embryos before they reach protected status at 5 days post fertilisation. Results demonstrate that human cancer cells actively invade within a zebrafish microenvironment, and form metastatic tumours at secondary tissue sites, suggesting that the mechanisms involved during the different stages of metastasis are conserved between humans and zebrafish, supporting the use of zebrafish embryos as a viable model of human cancer metastasis. We suggest that the embryonic zebrafish xenograft model of human cancer is a tractable laboratory model that can be used to understand cancer biology, and as a direct replacement of mice for the analysis of drugs that target cancer invasion and metastasis.Animal science

Generation of Constitutive Active ERK Mutants as Tools for Cancer Research in Zebrafish

Animal science

Characterization and expression patterns of the MAPK family in zebrafish

Animal science

Novel treatments of uveal melanoma identified with a synthetic lethal CRISPR/Cas9 screen

Animal science