THE ROLE OF EXTRACELLULAR VESICLES IN BREAST CANCER PROGRESSION AND DIAGNOSIS

Abstract

Breast cancer (BC) is the second most commonly occurring malignant disease in women and one of the leading causes of cancer-related death worldwide, globally accounting for almost half-a-million deaths per year. In Canada, BC is the second leading cause of death in women preceded only by lung cancer. Invasion and metastasis are the most common causes of mortality in patients with BC. Studies show that extracellular vesicles (EVs) play an important role in immune system evasion, invasion and metastasis. Studies have shown a significant elevation of EVs in the serum of cancer patients compared to healthy subjects. Furthermore, elevated secretion of EVs has been correlated with cancer malignancy. Therefore, it has been suggested that EVs may be an important non-invasive diagnostic and prognostic tool for cancer. Herein our in vitro studies show that ER-α is secreted via EVs from MCF-7 cells. Furthermore, our mass spectrometry (MS)-based proteomic study showed that the proteomic profile of EVs from the plasma of BC patients differs from that of healthy subjects. In addition, we have also shown that vesicular abundance of proteins associated with tumour malignancy, such as tissue factor (TF), plasminogen activator inhibitor (PAI-1), a disintegrin and metalloproteinase 12 (ADAM12) and β-Catenin is different between primary tumour and metastatic disease.