Abstract
Background. Multiple myeloma (MM) is a hematologic malignancy of plasma cells. The microenvironment plays a key role in MM cell survival and drug resistance through release of soluble factors, expression of adhesion molecules and release of exosomes (EXs). The role that EXs, released by MM cells have in cell-to-cell communication and signaling in the bone marrow is currently unknown. EXs as a source of markers for MM diagnostics are also not studied. Objective: to use proteomic profiling of EXs as a tool to identify circulating tumor associated markers in MM patients. Results. The proteome composition of EXs obtained from plasma of patients with MM and multiple sclerosis was studied for the first time. nano-HPLC–MS/MS analysis identified a total of 332 proteins in the EXs of both groups of patients and determined the proximity of their qualitative composition. For the first time, 12 differentially expressed proteins were detected, the levels of which were significantly increased in EXs from patients with MM. This allowed us to consider them as potential markers of the disease. Conclusion. Proteomic analysis of EXs obtained from plasma of patients with MM is an important method for finding disease markers.
Highlights
Multiple myeloma (MM) is a hematologic malignancy of plasma cells
The microenvironment plays a key role in MM cell survival and drug resistance through release of soluble factors, expression of adhesion molecules and release of exosomes (EXs)
The role that EXs, released by MM cells have in cell-to-cell communication and signaling in the bone marrow is currently unknown
Summary
Multiple myeloma (MM) is a hematologic malignancy of plasma cells. The microenvironment plays a key role in MM cell survival and drug resistance through release of soluble factors, expression of adhesion molecules and release of exosomes (EXs). Типирование и количественное определение ЭС методом иммуноферментного анализа (ELISA) проводили по методике производителя (System Biosciences (SBI), США). Подготовку образцов для протеомного картирования, анализ нано-ВЭЖХ-МС/МС и обработку полученных данных проводили по методикам, описанным ранее [8]. Вначале проводили центрифугирование плазмы крови на малой (1500g) скорости для удаления мертвых клеток и крупных продуктов апоптоза, а затем центрифугировали на более высоких (15 000g) скоростях, что позволяло удалять большие везикулы и продукты клеточного распада. Введенная нами дополнительно процедура фильтрования плазмы крови через 0,22 мкм фильтр избавляла от внеклеточных везикул с размером частиц >100 мкм и позволяла получать более чистые фракции ЭС. Полученные результаты показали, что из 332 белков 100 ранее были найдены непосредственно в ЭС, секретируемых разными клетками, 46 – во внеклеточных частицах плазмы крови человека, а 62 – в микрочастицах крови. Обычно представленные в экстраклеточных везикулах и идентифицированные в экзосомах плазмы крови больных множественной миеломой и рассеянным склерозом
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