Drosophila as a Model System to Study Nonautonomous Mechanisms Affecting Tumour Growth and Cell Death

Figure 1

Immune interactions between larval tumours and their microenvironment (TME). (a) In Drosophila larvae, where tumours are generated in imaginal discs (tumour in red), the TME consists mostly of immune cells (in green), the fat body (in orange), and the trachea (in purple). (b) The molecular interactions within the TME are represented in this figure. Positive effects on growth and/or proliferation are highlighted by lines ending in arrowheads, while lines ending in bars show negative effects, mostly represented by increased cell death. Solid lines indicate demonstrated interactions and dashed lines potential ones. Both the immune cells and the tumour produce the fly TNF homolog Egr. It acts as a double-edge sword depending on the context of the tumour, represented as the Ying-Yang paradigm. Egr is antitumour in scrib-group mutant contexts, while being protumour and prometastatic when is present in the scrib-group mutant genetic background. The effect of tumour-derived Egr on immune cells is still an open question. Egr is required to activate the Toll pathway in the fat body, which subsequently promotes tumour cell death in combination with Egr itself, through an unknown signal (question mark). The interleukin homolog Upd3 produced by the tumour induces immune cells proliferation, while immune cell-derived Upd3 promotes tumour proliferation and invasion. While tumour can promote tracheogenesis through incorporation of tumour cells into the tracheal wall (tracheal mimicry), the effects of trachea on tumour growth and metastasis remain elusive.