Seminar given by: Golam Kibria, B.Pharm., M.Pharm., Ph.D.
Research Assistant Professor
Department of Pharmacology
Feinberg School of Medicine
Abstract: Breast cancer is the leading cancer in women with an incidence rate of 1/8, and metastasis accounts for 90% deaths. Cancer stem cells (CSCs) represent a subset of cancer cells responsible for tumorigenesis, metastasis and therapy resistance. Early diagnosis of cancer, evaluation of CSCs, and prediction/prevention of metastasis hold the key for patient survival. Yet, there are many limitations to existing evaluation approaches using invasive biopsy-based molecular profiles. We recently developed a novel and easily accessible technology using non-invasive liquid biopsy of blood to profile circulating exosomes for new biomarker discoveries of breast cancer diagnosis and prognosis. Exosomes, cell- secreted vesicles (30-100 nm in diameter), carry different kinds of functional molecules (proteins, mRNAs, miRNAs, DNA), thus provide a promising approach to assess novel and dynamic biomarkers in human disease. A differential expression of breast CSC marker CD47 was shown on circulating exosomes from breast cancer patients versus those from healthy controls, that is correlated with breast cancer status, demonstrating a great potential of individual exosome profiles in biomarker discovery as well as future functional studies. Based on the proteomics of exosomes secreted by various human breast cancer cells, normal breast epithelial cells, breast cancer patient derived primary cells, as well as human mesenchymal stem cells, about 1500 total proteins were identified where an elevated expression of only 35 distinctive proteins including CD47, HER2 were found in cancer cell-derived exosomes. It is necessary and important to effectively monitor treatment response and predict recurrence and prognosis. Thus the functional characterization of exosomes related to stemness, invasiveness and metastasis would be effective to phenotypic cancer detection and prognostic studies in inhibiting breast tumor and its metastasis.
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