Understanding tumor metastasis in Drosophila Melanogaster model system

Cancer can be described as the uncontrolled growth of abnormal cells in an organism’s body, which occurs when the normal control systems in the body are malfunctioning. This produces a mass of the continually growing cells called a tumor. However, during tumor progression, the cancer cells through blood vessels migrate from the primary site of origin to secondary site where they affect another organ. This spreading of the cancer cells is called metastasis and makes treatment of cancer so difficult. Hence it is highly necessary to understand how the tumor metastasis happens and what is the role of normal cell in this process. Drosophila melanogaster commonly known as fruit fly has served as a useful model organism because of its well understood genome, availability of genetic tools and many evolutionarily conserved signaling pathways. Our understanding of the mechanisms regulating cell growth, differentiation and development has been considerably advanced by studies in Drosophila. Ras genes are associated with cell proliferation and overexpression of Ras protein leads to benign tumor in developing flies. Studies showed that suppressing cell polarity genes like Scrib induced neoplastic tumors. To model metastatic tumor, we co-activated the oncogene RasV12 and loss of polarity gene ScribRNAi in the wing imaginal disc. We used the UAS-GAL4 system to create the mutation in only few cells that will become invasive while remaining cells are normal in their genetic makeup. We hypothesize that these non-mutated normal cells and mutated cells interact among each other through signaling pathways to promote the tumor metastasis. To evaluate this we study the changes the key signaling pathways and metastatic markers like JNK, MMP1, Eiger through immunohistochemistry. We present our recent findings on this