Grant: Travel Awards - Institute Community Support

Bladder cancer (BC) most often presents as non-invasive tumors that protrude harmlessly into the bladder.  However, approximately 25% of these cancers will invade into the bladder wall, which can progress and spread to deeply invasive life-threatening disease. This project will investigate early invasion events, using a newly proposed safeguard mechanism that restrains invasion in early BC, but is lost as a critical step in progression of the disease. Proteins called "hedgehog" and "bone morphogenetic proteins" are proposed to operate predominantly in benign supporting tissue (stroma) next to BC and strongly oppose tumour invasion. We found suitable public databases to explore this hypothesis using human BC tumor tissue. However, there is a lack of such databases for the corresponding stromal tissue, leaving the role of stromal signaling in early stage human BC unexplored.  To investigate the application of this signaling model in clinical practice, we analyzed molecular data from 457 early stage human BC papillary tumors and identified 101 genes that were differentially expressed in early stage tumors. Additional computational analysis identified eight of these genes operate within a previously described "hedgehog-regulated" pathway. To better understand the role of stromal signaling in early stage human BC invasion, we will thoroughly analyze all proteins in human BC and stroma using a cutting-edge technology called comprehensive proteomics. This data will form the basis for new tests for physicians to more accurately recognize invasion in BC biopsies, leading to more accurate diagnoses and appropriate treatment.