RasV12 drives tumour proliferation in a Drosophila melanogaster lung tumour model

To study the contribution of the tumour microenvironment, the mechanisms underlying the actions of the tumour on the organism, and to identify anti-tumour drugs, allogeneic tumour models have been developed in different animals, including mice, rabbits, dogs, and Drosophila. In Drosophila, the same oncogenes known from human lung tumours can induce tumours in the airway system of the fly. The tumour driver RasV12 induces massive Drosophila airway progenitor cells (tracheoblasts) proliferation. Once induced, these cells proliferate uncontrolled, can no longer establish a normal airway system, and the animals finally die. Allogeneic transplantation is a suitable approach to studying the effects of different tumour environments. In Drosophila, injecting tissue into the adult body cavity and following their development is particularly easy because these cells are concurrently labeled with GFP. Airway progenitor cells with proliferative ability were used as donors and transplanted into different strains of Drosophila. I found that airway tumour cells could proliferate in the new host and affect the performance and survival of the host. Here, cells derived from the air sac primordium were more effective than those derived from the abdominal spiracular branch tracheoblasts. Retransplantation into an additional host showed the persistence of the cancerogenic properties of these allografts. Using different hosts, such as those deficient in producing the most important effectors of the innate immune system, the antimicrobial peptides, showed that these antimicrobial peptides are essential in fighting tumours. In addition, MEK inhibitors could partially rescue this proliferative phenotype. With this newly established model, I aim to study the microenvironment of tumour cells in vivo, simulate tumour metastasis, and study the interaction between the immune system and tumours.