Протеогликаны в нормальной физиологии и канцерогенезе

Появление и развитие злокачественных опухолей связано с многочисленными нарушениями физиологии клетки как на геномном, так и на белковом уровнях и затрагивает множество макромолекул, вовлеченных в различные аспекты ее жизнедеятельности. Однако рост злокачественной опухоли и ее метастазирование определяются не только молекулярными характеристиками самой опухолевой клетки, но и ее взаимодействием с окружающим внеклеточным матриксом (ВКМ) – важной и необходимой частью любой ткани. Огромную роль при этом играют сложные белково-углеводные молекулы протеогликанов (ПГ), которые являются одним из основных компонентов ВКМ и присутствуют на поверхности практически всех клеток, во многом определяя межклеточные взаимодействия и взаимодействия клеток с ВКМ. В процессе канцерогенеза происходят значительные нарушения структуры и состава ПГ, которые приводят к нарушению таких взаимодействий и инициируют трансформацию нормального ВКМ в опухолевое микроокружение, максимально адаптированное для поддержания роста опухолевых клеток, развития злокачественной опухоли и распространения патологического процесса путем метастазирования. В настоящее время множество ключевых ПГ идентифицированы как перспективные диагностические и прогностические молекулярные маркеры и целевые молекулы для создания новых противоопухолевых препаратов.

В обзоре рассматриваются основные классы ПГ, их структура, локализация, функциональная роль в нормальных тканях и участие в молекулярных механизмах злокачественной трансформации клеток и прогрессирования опухоли.

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