Abstract
The zebrafish is now an important model organism for cancer biology studies and provides unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level, providing novel insights into our understanding of cancer. Here we summarise the available transgenic zebrafish tumour models and discuss what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response towards transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour-associated macrophages and neutrophils in mammalian models and present evidence that supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to the signals that mediate leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells in zebrafish appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention.
Highlights
It has been well documented by pathologists that tumour masses are often densely packed with cells of both adaptive and innate arms of the immune system
We describe the studies conducted in zebrafish that have allowed the field to establish the significance of early host inflammatory responses in promoting cancer development at the pre-neoplastic stage, with a focus on innate myeloid cells
This review focuses upon the use of zebrafish for the study of tumour initiation, while the application of zebrafish for the study of metastasis has been reviewed by Osmani and Goetz, 2019 [28]
Summary
It has been well documented by pathologists that tumour masses are often densely packed with cells of both adaptive and innate arms of the immune system. It is only in recent years that in vivo live imaging studies have captured the initial inflammatory response to tumour initiation; revealing the rapid recruitment of macrophages and neutrophils in response to the oncogenic transformation of pre-neoplastic cells (PNCs) [6]. These studies show that this intrinsic inflammation begins to exert a trophic influence on PNC growth even at this nascent stage of cancer development [6,7]. B-Raf); HRAS (Harvey rat sarcoma viral oncogene homolog); NRAS (neuroblastoma RAS viral oncogene homolog); PTTG (pituitary tumour transforming gene)
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