組織の曲線とアピコバサルの機械的緊張の不均衡は,癌の形態変異を指示する

Hendrik A Messal¹, Silvanus Alt^2,3, Rute M M Ferreira^1,4

¹Adult Stem Cell Laboratory, The Francis Crick Institute, London, UK.

Nature

|February 1, 2019

まとめ

管状臓器の腫瘍の形状は癌細胞が細胞骨格と元の管の大きさをどのように変化させるかに依存しますこの発見は臓のような臓器における皮質がんの成長を理解するのに役立ちます

科学分野:

バイオ物理学
癌生物学
オルガノイド開発

背景:

管状上皮は臓器を形成し,がんの頻発部位である.
腫瘍発生は細胞の過剰増殖と組織構造の破壊を含みます
異常な腫瘍の形状を制御する生体物理的要因は不明である.

研究の目的:

皮質腫瘍の形状を決定する生理学的パラメータを調査する.
臓管の癌発症時の形態学的変化を分析する.
細胞のメカニズムと組織の幾何学との相互作用を理解する

主な方法:

単細胞解像度組織分析のための3D全臓器画像技術を開発しました.
マウスの臓管の腫瘍性変異を研究した.
3D頂点モデルのシミュレーションと皮質力学の連続体理論を活用した.

主要な成果:

発がん性変異は,外生性および内生性腫瘍の増殖を誘発した.
変形した細胞で観察されたアピカル・ベース・ミオシン活性グラデントの喪失.
源頭上皮質の直径は腫瘍の形状を決定する.小管は外生体成長,大管は内生体成長を生成する.
緊張の不均衡と組織の曲線が決定的な要因として特定されました

結論:

皮質腫瘍の形態は,変形した細胞と元の管状幾何学による変化によって支配される.
発見は臓,肝臓,肺管状表皮に一致する.
この研究は皮質腫瘍形成に関する根本的な洞察を提供します

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