Cellular communication and interactions are critical and essential for the sustenance and progression of complex diseases like cancer. The involvement of peritoneal microenvironment is even more striking with a preponderance of transcoelomic metastasis in epithelial ovarian cancer. Albeit omentum, a fold of inner peritoneum made up of fatty-tissue, is the most common site of ovarian metastasis, there is a heterogeneity in the distribution of metastatic foci indicating a possible underlying modulator in the omental mesothelial cells. Also, there is a potential cell-to-cell interaction that implies a possible involvement of Notch-3, a well-known juxtacrine signalling pathway.
In order to study whether a potential differential activation of Notch-3 in the tumor cells by the heterogeneous ligand expression (Jag-1) in mesothelial cells can lead to further disease progression and altered drug sensitivity, a luciferase-based reporter sensor platform has been developed along with differential cellular clones of jagged-1 mimicking the in vivo scenario. I am also investigating the effect of activated Notch-3 on different cellular phenotypes through functional assays.