Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

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.

Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges

“…A direct connection between inflammation and cancer is that tissue injury, and the concomitantly produced inflammatory factors, promote cancer cell growth via dysfunction in chemokine and cytokine signaling [4]. It is known that some cancer types rely on inflammatory signals for their progression, angiogenesis, proliferation and survival, invasiveness and metastasis [5][6][7]. Therefore, targeting inflammation is a promising therapeutic option for those types of cancers.…”

Tipping the Scales With Zebrafish to Understand Adaptive Tumor Immunity

“…Through exhaustive comparison of the human and zebrafish genome assemblies, it was found that 82% of disease-causing human genes have at least one zebrafish ortholog ( Howe et al, 2013 ). This level of conservation has led to the development of a wide array of cancer models in zebrafish ( Casey and Stewart, 2018 ; Hason and Bartůněk, 2019 ; Casey and Stewart, 2020 ; Elliot, 2020 ). Through the years of ongoing research, the pathological similarities of cancer and preservation of the immune components have also been well established between zebrafish and humans.…”

Anti-tumour drugs of marine origin currently at various stages of clinical trials (review)

“…Annually, 1,000 new molecules are being isolated from marine organisms, many of which have complex molecular structure, contain many potentially bioactive groups with so far undetermined mechanism of action (Van Andel et al, 2018). Marine organisms are used not only to obtain biologically active combinations, but in some cases as experimental models with unique experimental properties that provide additional possibilities for modeling and studying the biology of cancer (Elliot et al, 2020). Active interaction between representatives of various directions of science, medicine and industry would allow an effective implementation of all the stages of obtaining the final pharmaceutical product from marine organisms starting from the moment of discovery to use in practiceidentification of combinations, determining their biological activity, chemical synthesis, development of methods of targeted transport, clinical trials, to introduction into production (Newman, 2016;Barreca et al, 2020).…”