84 4 The Infection - Induced Proteolysis of The Receptor PGRP - LC Activates the IMD

1 Immune response to tumors in Drosophila. José C. Pastor-Pareja, Ming Wu, Tian Xu. Howard Hughes Medical Institute, Dept. of Genetics, Yale University School of Medicine, New Haven, CT. We use Drosophila to study cancer biology. In our laboratory, several genome-wide screens for mutations that promote tumor progression and metastasis have been performed. Fly tumors mutant for the polarity determinant scribble that express an oncogenic form of Ras at the same time (RasV12/scrib-/-) exhibit malignant behavior similar to that observed in human metastatic cancers. Features of these tumors include accelerated growth, loss of cell adhesion, basement membrane degradation, migration and invasion, as well as secondary tumor formation. Recently, we have discovered that flies are able to mount an immune response to RasV12/scrib-/tumors. We are investigating this response and have found so far that tumors activate hemocytes and that hemocytes, in turn, adhere to tumors and affect their growth. We are currently adressing the molecular mechanisms underlying these phenomena and will present our initial findings regarding signaling between tumors and hemocytes and how hemocytes recognize tumors. This Drosophila model provides a tool for dissecting the genetic, molecular and cellular mechanisms of tumor-immune system interactions.