López-Cuevas Paco, Cross Stephen J, Martin Paul
School of Biochemistry, University of Bristol, Bristol, United Kingdom.
Wolfson Bioimaging Facility, University of Bristol, Bristol, United Kingdom.
Front Cell Dev Biol. 2021 Apr 30;9:676193. doi: 10.3389/fcell.2021.676193. eCollection 2021.
The zebrafish () 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.
斑马鱼（）最近已成为研究癌症生物学和肿瘤微环境的优秀模型，包括对伤口和早期癌症生长的早期炎症反应。在这里，我们使用半透明斑马鱼幼虫的高分辨率共聚焦成像，结合新型自动跟踪和细胞：细胞相互作用软件，来研究先天免疫细胞如何与表达突变活性人类癌基因（HRASG12V）的修复伤口和早期癌症（癌前）细胞相互作用。我们发现，全身或局部递送的细菌感染会导致募集到急性伤口和癌前细胞的中性粒细胞和巨噬细胞数量及行为发生变化，并且感染会以导致伤口愈合显著延迟和癌前细胞数量减少的方式改变细胞相互作用。除了提供关于科利毒素和其他癌症细菌疗法如何发挥作用以减轻癌症负担的见解外，我们的研究还突出了可轻松适用于研究其他斑马鱼模型中细胞行为和相互作用的新型软件工具。
