乳がん転移のメカニズムを発見、治療のターゲットに(Mechanics of breast cancer metastasis discovered, offering target for treatment)

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2023-10-27 ペンシルベニア州立大学(PennState)

◆新たな研究が、乳がん細胞の転移メカニズムを解明し、乳がん細胞の運動に関与するダイニンと呼ばれるモータープロテインを特定しました。この発見は、転移の新しい治療標的を提供し、がん治療のアプローチを変える可能性があります。
◆研究者は、乳がん細胞の動きを観察し、ダイニンががん細胞の運動に重要な役割を果たすことを明らかにしました。ダイニンを標的にすることで、がん細胞の運動を阻止でき、転移を制御する新しい方法が示唆されています。
◆このアプローチは、化学療法や放射線療法のように健康な組織に損傷を与えずに、がん細胞の転移を防ぐことができる可能性があります。ただし、臨床応用にはまだ時間がかかるため、人間や動物での試験が必要です。

<関連情報>

ダイニンを動力源とする細胞運動が乳がんの転移を導く Dynein-Powered Cell Locomotion Guides Metastasis of Breast Cancer

Yerbol Tagay, Sina Kheirabadi, Zaman Ataie, Rakesh K. Singh, Olivia Prince, Ashley Nguyen, Alexander S. Zhovmer, Xuefei Ma, Amir Sheikhi, Denis Tsygankov, Erdem D. Tabdanov
Advanced Science  Published: 19 September 2023
DOI:https://doi.org/10.1002/advs.202302229

Details are in the caption following the image

Abstract

The principal cause of death in cancer patients is metastasis, which remains an unresolved problem. Conventionally, metastatic dissemination is linked to actomyosin-driven cell locomotion. However, the locomotion of cancer cells often does not strictly line up with the measured actomyosin forces. Here, a complementary mechanism of metastatic locomotion powered by dynein-generated forces is identified. These forces arise within a non-stretchable microtubule network and drive persistent contact guidance of migrating cancer cells along the biomimetic collagen fibers. It is also shown that the dynein-powered locomotion becomes indispensable during invasive 3D migration within a tissue-like luminal network formed by spatially confining granular hydrogel scaffolds (GHS) made up of microscale hydrogel particles (microgels). These results indicate that the complementary motricity mediated by dynein is always necessary and, in certain instances, sufficient for disseminating metastatic breast cancer cells. These findings advance the fundamental understanding of cell locomotion mechanisms and expand the spectrum of clinical targets against metastasis.

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