Как остановить рост опухоли?

ДЛЯ ТОГО чтобы опухоль разрослась и диаметр ее превысил 1—2 мм, в ней должна образоваться собственная сеть кровеносных сосудов. К такому выводу пришел в 1961 г. Дж.Фолкман (в то время сотрудник Института медицинских исследований ВМФ США). Но если это действительно так, то препараты, ингибирующие ангиогенез, т.е. формирование сосудов, должны подавлять опухолевый рост. Последующие 20 лет Фолкман, работая в Медицинской школе Гарвардского университета, занимался поисками опухолевого ангиогенного фактора: он предполагал, что в солидных опухолях рост пронизывающих опухолевую ткань сосудов происходит под влиянием образуемого самими опухолевыми клетками вещества, стимулирующего размножение эндотелиальных клеток, из которых формируются капилляры. Недавно Фолкман и его коллеги выделили и очистили этот фактор; найден также способ ингибировать его активность.

Для проверки своей гипотезы Фолкман и его сотрудники разработали новые методики выращивания опухолей в среде, изолированной от кровеносных сосудов (в диффузионной камере или в без сосудистой ткани), и эндотелиальных клеток в культуре. Потребовалось несколько лет, чтобы твердо установить, что опухоли действительно секретируют растворимый фактор роста эндотелиальных клеток, стимулирующий антиогенез. Однако получить его в очищенном виде долго не удавалось. Идея способа очистки возникла, когда в лаборатории Фолкмана было обнаружено, что гепарин способствует миграции эндотелиальных клеток и этим ускоряет образование сосудов.

Гепарин — это полисахарид, содержащийся во многих тканях. В медицине

гепарин широко применяется в качестве антикоагулянта. Ю. Шинг и М. Клагсбрун предположили, что гепарин стимулирует ангиогенез, увеличивая концентрацию фактора роста у поверхности эндотелиальных клеток. Они решили воспользоваться вероятным сродством фактора роста к гепарину. В колонке для гельфильтрации гранулы геля покрыли гепарином и пропустили через них частично очищенный препарат фактора, выделенного из хондросаркомы (опухоли хрящевой ткани). Большая часть смеси прошла сквозь колонку, а то, что осталось в ней, было отделено от гепарина и проанализировано с помощью метода гель-электрофореза (при этом белки разделяются в соответствии с их размерами). Искомый фактор представляет собой небольшой белок, который оказался мощным стимулятором роста эндотелиальных клеток и ангиогенеза.

Шинг и Клагсбрун считают, что вещество, полученное из хондросаркомы, является естественным фактором роста нормальной хрящевой ткани, где он стимулирует васкуляризацию, происходящую при превращении хряща в кость. Другими словами, опухолевый ангиогенный фактор не специфичен для опухолевых клеток — это обычный для организма фактор роста, который по какой-то причине вступает в действие не вовремя или функционирует слишком долго.

Гепарин, как выяснилось, может играть роль не только стимулятора ангиогенеза, но и его ингибитора. С.Тей- лор, изучая образование сосудов на мембране куриного эмбриона, с целью предотвратить воспаление, добавлял к гепарину гормон кортизон. Вокруг места, пропитанного смесью гепарина и кортизона, эмбриональные кровеносные сосуды претерпевали обратное развитие, и ангиогенез прекращался. По отдельности эти два вещества не имели такого эффекта. Если мышей заставить съесть смесь гепарина с кортизоном, у них наблюдается уменьшение размеров некоторых опухолей.

 

 

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