Grant: Master's Award: Canada Graduate Scholarships

Cancer cells which migrate from one place to another throughout the body, called metastatic cancer cells, are one of the major causes of death in cancer, especially breast cancer. To metastasize, cancer cells must first change from their initial rounded epithelial (E) state to a starfish-like mesenchymal (M) state. Then, to establish new tumours, the reverse change occurs. Fat cells, called adipocytes, are known to influence this process, and may explain why obese patients have higher rates of metastasis. Our lab showed that fat cells can cause certain breast cancer cells to shift from their initial M state to a state in between M and E, an E/M state. This occurs only in the presence of an extracellular matrix (ECM) proteins. Exactly how fat cells cause this change is unknown, but we have narrowed it down to 6 adipocyte-secreted ECM-induced proteins. Over the course of this project, I aim to assess the relevance of the adipocyte-induced E/M shift of breast cancer cells in metastasis. This is broken down into two aims: determining which protein is responsible for the E/M shift and measuring the presence of said protein in metastatic sites. For the first aim, addition and blocking of the proteins in BC cell cultures will be used. This will be done through a combination of blocking antibodies, gene silencing and addition of the proteins to breast cancer cells alone. For the second aim, bone marrow metastases from mice implanted with patient-derived breast cancer cells will be tested for the presence of the culprit protein. The presence of E/M shift causing proteins in metastatic sites will strengthen the link between our observations and human metastasis. Identification of which proteins cause an E/M shift in BC cells can reveal new avenues of therapy to limit metastasis.