Investigating the role of inflammatory cytokines on tumor progression and metastasis in a Drosophila cancer model
Tumor cells and surrounding normal cells interact with each other and constitute the tumor microenvironment (TME) which supports the survival and proliferation of tumors. Studies indicate the presence of inflammatory components in the TME. However, little is known about the effect of these inflammatory molecules on tumor growth and progression. The core inflammatory pathways are conserved in Drosophila. Imaginal discs of Drosophila melanogaster are a popular model to study epithelial tumors due to the variety of mosaic analysis tools, and the ease positively marking cells that allow tracking growth and progression of tumor cells. We co-activated oncogenic forms of Yki or RasV12 activities in polarity deficient (scribble mutant) epithelial cells to model aggressively growing and metastatic tumors. To simulate the TME, ‘FLP-out’ clones of tumor cells marked with GFP were generated. The activity of key inflammatory pathways Toll, TNF, and JNK in the TME was tested by immunohistochemistry. We observed upregulation of Cactus (TLR pathway component) and p- JNK (activated form of JNK), and downregulation of Drosophila TNF ligand, Eiger in the tumor cells. Of these, only Eiger was upregulated in neighboring normal cells. Based on these results we hypothesized that a bidirectional cross-talk between the tumor and normal cells in the TME elicits a differential inflammatory response that promotes tumor cell survival and progression. To analyze this, we down-regulated Cactus and Wengen (TNF receptor) and evaluated the effect on tumor size and survival of tumor cells. A comparison of hyperplastic (Yki ScribRNAi) and metastatic (RasV12 ScribRNAi) tumor model was done to identify the role of inflammatory cytokines in tumor progression. Here, we report our progress on the study of the effect of these pathways and inflammatory cytokines on tumor survival and metastasis. Our research will help unravel the correlation between inflammatory pathways and tumor progression in an in vivo model.
Graduate Research - Graduate
Madhuri Kango-Singh, Amit Singh
Primary Advisor's Department
Stander Symposium poster
"Investigating the role of inflammatory cytokines on tumor progression and metastasis in a Drosophila cancer model" (2017). Stander Symposium Posters. 943.