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Page 8 of 11 Tulotta et al. J Cancer Metastasis Treat 2019;5:74 I http://dx.doi.org/10.20517/2394-4722.2019.022

with primary tumours are treated, when possible, with surgery. However, metastasis can occur years
[100]
after surgical intervention . Metastatic cancer associates with poor patient prognosis and represent a
major challenge for clinical research. Chemotherapy is often the pharmacological choice to treat cancer,
although side effects alter normal cell physiology and affect patient life quality. Moreover, cancer relapse
and therapy resistance associate with poor prognosis. Progress in biomedical research has shown that
targeting cancer cells is not the only therapeutic option. The interaction between tumour and surrounding
stroma supports cancer survival and spreading, representing therefore a possible new treatment
[101]
strategy . Here, we describe the use of the zebrafish xenograft model to study early stages of experimental
micrometastasis formation, engrafting fluorescent tumour cells in transparent zebrafish embryos with
fluorescent endothelial and immune cells. We propose that targeting CXCR4 signalling on cancer cells or
in the tumour microenvironment is a valid approach to inhibit metastatic cancer and suggest that anti-
CXCR4 therapy might have double treatment benefits. In addition, therapeutic modulation of the immune
system might result in the reinforcement of the immune defence against cancer. However, we suggest that
treatments designed to target malignant cells might affect tumour microenvironment intrinsic functions.
Specifically, the intrinsic physiological role of myeloid cells can be affected by cancer treatment, resulting
in an inability to mount a functional anti-cancer response or, on the other hand, in the ability to mount a
tumour-supportive response.

DECLARATIONS
Authors’ contributions
Wrote and reviewed the manuscript: Tulotta C, Snaar-Jagalska BE

Availability of data and materials
Not applicable.

Financial support and sponsorship
The work was supported by the Netherlands Organization for Scientific Research (TOP GO Grant:
854.10.012).

Conflicts of interest
Both authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.

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