Project 458297

Every year, there are about 20 million new cancer cases and about 10 million cancer deaths. This devastating disease, which is caused by mutation and abnormal proliferation of cells, often leads to the cancerous cells losing their connections with the extracellular environment, travelling through the body via the blood or lymphatic vessels and establishing a new tumour in a new location, a process called metastasis. Metastasis accounts for 90% of the cancer deaths. Despite the cancer cells metastasizing into almost every organ in the body, cardiac invasion accounts for less than 1% of the metastasis events. Even in these rare cases, cancer is often non-malignant and is not the cause of death. These observations indicates that there are factors that are potentially protecting the cardiac tissue from cancer invasion. I propose that the observed resistance of the cardiac tissue to cancerous cells lies within the biophysical environment of the cardiac tissue and that extracellular vesicles (EVs) secreted by the cardiac tissue play an essential role in this process. Due to the complexity of the system, I plan to study these factors in an in vitro organ-on-a-chip system. For my studies, I will need to: a) develop a 3D vascularized in vitro design that connects the cardiac tissue to cancer tissue via vascularized vessels. b) study the effects of biophysical factors such as electrical stimulation and mechanical stretching on the tissue. c) evaluate microRNA and RNA cargo profiles of the EVs secreted by cancerous tissue and cardiac tissue, when cultivated separately or in combination. This project will enable me to shed light into the physiological mechanisms that shield cardiac tissue from cancer invasion. These identified factors will give us tools that will enable new approaches for cancer therapies.