Live imaging of signalling events during wound repair and tumour induced inflammation in a zebrafish model

The idea that "tumors are wounds that do not heal” was first postulated by Dr Harold Dvorak, based on the similarities between tumour stroma generation and wound healing. Since then there have been numerous studies suggesting that tumour stroma largely resembles wound stroma, sharing similar transcriptome and harbouring similar cellular components. Many signals that have been shown to be up-regulated during wound repair are also reported to be activated in the tumour stroma compartment. Therefore, it is plausible that signals released during wound healing might play a promotive role for tumourigenesis. There are many reports indicating that some tumours might arise from wounded tissue. So can host tissue repair machinery be promotive for tumourigenesis when there are pre-existing pre-neoplastic cells in the tissue and what signals might be involved in the process?
Until recently, it was not possible to live image the earliest interactions between host and oncogene-transformed pre-neoplastic cells during tumour initiation. Earlier work in the lab using zebrafish as model organism has made it possible to visualize a pre-neoplastic cell at its inception in vivo, and has revealed that the transformed cell elicits a Trophic Inflammatory response, in which recruited leukocytes promote transformed cell growth, at least in part, through COX-2 mediated PGE2 production.
Taking advantage of our zebrafish inducible tumourigenesis model and live imaging approach we will test whether tissue repair processes might lead to an increase in tumourigenesis. We will also test what factors might be released during wound healing that might be promoting pre-neoplastic cell growth. Finally we will use reporter lines for NFkB pathway to address the involvement of NFkB signaling during tumour initiation and tissue repair and whether activation of NFkB pathway is involved in the wound induced tumour promotion.
This project would provide important implications for cancer surgery, which is still the first line of treatment currently for most solid tumours.

TECHNIQUES INVOLVED:

Zebrafish genetics; confocal microscopy; live imaging of zebrafish larvae; time-lapse imaging analysis using Velocity and Image J software; DNA purification & in vitro transcription of Capped-RNA for embryo injection; zebrafish embryo micro-injection; wholemount immuno-staining.