XXXIV/252. Mass spectrometry analysis of extracellular vesicles from malignant ascites highlights the role of tumor microenvironment in progression of ovarian cancer
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| Year of publication | 2022 |
| Type | Conference abstract |
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| Citation | |
| Description | Ovarian cancer (OC) ranks among the deadliest cancers in women. Lack of clear symptoms, rapid spread of metastases and common chemoresistance all contribute to unfortunate fate of majority of ovarian cancer patients, especially those having the high-grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common type of OC. Many of HGSC patients have excess fluid in the peritoneum at the stage of diagnosis called ascites. Ascites is basically a tumor microenvironment in the liquid form containing various cells, proteins and other molecules and also extracellular vesicles (EVs). EVs are small membrane-bound particles that convey proteins, lipids and nucleic acids between cells and their cargo reflects the cell of the origin. EVs play important role in cancerogenesis and hold a great promise as disease biomarkers as well as potential therapeutic targets. Small size and polydispersity of EVs brings various challenges to their isolation, including method-dependent contaminants. We isolated EVs from ascites by two different methods and analyzed them by advanced mass spectrometry; only proteins identified in both preparations for each patient were further considered. We identified “true ascitic EV proteome” consisting of 2,418 proteins, which contains typical EV markers, is devoid of proteins routinely contaminating EV isolates, and covers interpatient heterogeneity. Next, we compared this proteome with EVs from related control fluids and found 74 proteins present only on EVs from HGSC patients. We believe that this list of proteins contain both important players of HGSC progression as well as potential biomarkers. Then, using scRNA sequencing data, we mapped the origin of EVs to different types of cells present in malignant ascites. Our results suggest that EVs in ascites do not come predominantly from tumor cells as was expected, but rather from a variety of non-malignant cell types including cancer-associated fibroblasts and tumor-associated macrophages. This emphasizes the recently appreciated role of tumor microenvironment in the progression of HGSC and lays foundations for further experiments |
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