The zebrafish (Danio rerio) has recently emerged as an excellent model to study cancer biology and the tumour microenvironment, including the early inflammatory response to both wounding and early cancer growth. Here, we use high-resolution confocal imaging of translucent zebrafish larvae, with novel automated tracking and cell:cell interaction software, to investigate how innate immune cells behave and interact with repairing wounds and early cancer (pre-neoplastic) cells expressing a mutant active human oncogene (HRASG12V). We show that bacterial infections, delivered either systemically or locally, induce a change in the number and behaviour of neutrophils and macrophages recruited to acute wounds and to pre-neoplastic cells, and that infection can modify cellular interactions in ways that lead to a significant delay in wound healing and a reduction in the number of pre-neoplastic cells. Besides offering insights as to how Coley’s toxins and other cancer bacteriotherapies may function to reduce cancer burden, our study also highlights novel software tools that can be easily adapted to investigate cellular behaviours and interactions in other zebrafish models.
Bibliographical noteFunding Information:
We thank Yi Feng and Nikolay Ogryzko for sharing the zebrafish line Tg(mpeg1:nls-Clover), Will Wood for the gift of DsRed E. coli, members of PM?s, Rebecca Richardson?s, and Chrissy Hammond?s labs for helpful discussion, Jon Palacios-Filardo for input into data analysis, and David Gurevich, Lucy MacCarthy-Morrogh, and Yi Feng for reading drafts of our manuscript. We also thank members of the Wolfson Bioimaging Facility (University of Bristol, United Kingdom) for their help with imaging and image analysis, and the Zebrafish Facility of the University of Bristol for their services and contribution. Some schematic representations were in part generated with the support of Biorender. Funding. PL-C was funded by the Spanish Rafael del Pino Foundation, and by a generous Bristol Cancer Bequest. SJC was funded by the Elizabeth Blackwell Institute, through its Wellcome Trust ISSF Award. PM was funded by a Wellcome Trust Investigator Award (WT:217169/Z/19/Z).
PL-C was funded by the Spanish Rafael del Pino Foundation, and by a generous Bristol Cancer Bequest. SJC was funded by the Elizabeth Blackwell Institute, through its Wellcome Trust ISSF Award. PM was funded by a Wellcome Trust Investigator Award (WT:217169/Z/19/Z).
© Copyright © 2021 López-Cuevas, Cross and Martin.