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Tulotta et al. J Cancer Metastasis Treat 2019;5:74 Journal of Cancer
DOI: 10.20517/2394-4722.2019.022 Metastasis and Treatment

Review Open Access

CXCR4 signalling, metastasis and immunotherapy:
zebrafish xenograft model as translational tool for

anti-cancer discovery

Claudia Tulotta, B. Ewa Snaar-Jagalska

IBL Animal Sciences & Health, Institute of Biology Leiden, Leiden University, Leiden, CC 2333, the Netherlands.

Correspondence to: Dr. B. Ewa Snaar-Jagalska, IBL Animal Sciences & Health, Institute of Biology Leiden, Leiden University,
Einsteinweg 55, Leiden, CC 2333, the Netherlands. E-mail: b.e.snaar-jagalska@biology.leidenuniv.nl

How to cite this article: Tulotta C, Snaar-Jagalska BE. CXCR4 signalling, metastasis and immunotherapy: zebrafish xenograft
model as translational tool for anti-cancer discovery. J Cancer Metastasis Treat 2019;5:74.
http://dx.doi.org/10.20517/2394-4722.2019.022
Received: 14 Aug 2019 First Decision: 20 Sep 2019 Revised: 18 Oct 2019 Accepted: 31 Oct 2019 Published: 8 Nov 2019

Science Editor: Pravin D. Potdar Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Cell-to-cell communication guarantees homeostasis in a multi-cellular organism. Cancer-to-microenvironment
communication sustains malignant growth and dissemination. Whereas the accumulation of mutations is at the
origin of malignant cell transformation and neoplasia onset, the interaction between cancer and the surrounding
stroma, specifically immune cells, influences the balance between tumour regression and tumour progression. To
study how the interaction between cancer and stromal cells is disadvantageous or beneficial for tumour progression,
the use of a transparent in vivo model bears important research potentials. Zebrafish has been increasingly used as
animal model to study tumour biology. The use of transparent zebrafish embryos, with fluorescent endothelial and
immune cells, allows the visualization of cell-to-cell interaction, among host cells themselves and between zebrafish
stroma and implanted human cancer cells. Here, we summarise our findings on the role of CXCR4 signalling in
tumour progression, considering its signature both on cell autonomous and host dependent mechanisms. Finally,
we address the translational impact of targeting CXCR4 signalling in cancer and the tumour microenvironment for
the treatment of metastatic cancer.

Keywords: CXCR4, cancer, metastasis, neutrophils, zebrafish, immunotherapy

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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