Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, primarily due to metastatic spread of the disease [1-4]. A growing body of research indicates that neutrophils, which are important elements of the tumour microenvironment (TME), may either stimulate or inhibit the complicated, multi-step process of metastasis [5-7]. However, the mechanisms by which neutrophils influence CRC metastasis, especially through chemokine-mediated recruitment, are not fully understood.
To study these interactions, we are using a novel optically translucent immunocompromised zebrafish model (CasperSCID) for in vivo real-time imaging of CRC cell metastatic behaviour [8]. To facilitate visualization of tumour-neutrophil interactions by confocal microscopy, we generated CasperSCID/mpx:GFP animals, whose neutrophils are fluorescently labelled. Human CRC cell lines with varying metastatic potentials were xenografted into these zebrafish, allowing for the real-time tracking of neutrophil dynamics in both primary and metastatic sites.
Preliminary observations suggest that CRC cell lines vary in their ability to establish primary and secondary tumours. We are now exploring if differential neutrophil recruitment contributes to these phenotypes and the role of different tumour-derived chemokines in promoting or suppressing metastasis. These studies are expected to provide insight into how specific chemokines modulate neutrophil function in tumours and the impact that this has on tumour growth and metastasis.