微環境的自己消化が腫瘍の成長を促す

Nadja S Katheder^1,2, Rojyar Khezri^1,2, Fergal O'Farrell^1,2

¹Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, N-0379 Oslo, Norway.

Nature

|January 13, 2017

まとめ

悪性腫瘍は周囲の細胞で栄養素のリサイクルプロセスである自閉症を活性化しますオートファギーの抑制は腫瘍の成長を抑制し,早期の腫瘍発育と微小環境の相互作用における重要な役割を強調する.

科学分野:

細胞生物学
腫瘍学
発達生物学

背景:

悪性腫瘍はマイクロ環境と相互作用し飢餓中に栄養素を供給するプロセスである自動食を活性化します
腫瘍による自己死性の調節と,腫瘍の成長に対するその影響は,依然として議論の余地がある.
腫瘍と微小環境の相互作用を理解することは,がん研究にとって極めて重要です.

研究の目的:

ドロソフィラ・メラノガスターモデルを使用して,腫瘍の成長と微小環境の相互作用におけるオートファギーの役割を調査する.
腫瘍の微小環境と全身的にオートファギーを誘発するかどうかを判断する.
治療戦略として自己消化抑制剤の可能性を評価する.

主な方法:

ドロソフィラ・メラノガスターの悪性腫瘍モデルを使用した.
腫瘍の微小環境と全身的に非細胞自律的自己消化誘導を調査した.
薬学的な抑制とオートファジー経路の遺伝的操作を用い
アミノ酸の輸送を含む腫瘍の成長,侵入,代謝活動を分析した.

主要な成果:

非細胞自律的オートファギーは,腫瘍の微小環境と遠隔組織の両方で誘発されます.
薬理学的なオートファギーの抑制は,腫瘍の成長を著しく抑制する.
初期段階の腫瘍の成長と侵入は,局所的な微生物環境内のオートファジーに依存しています.
腫瘍誘発的自は,ドロソフィラの腫瘍死滅因子とIL-6のようなシグナル伝達によって媒介されます.
腫瘍の成長はアミノ酸の輸送に依存しています
自閉症の動物からの不活性な腫瘍は自閉症の熟練した宿主に移植されたときに再び成長します

結論:

変異した細胞は周囲の正常な細胞と接触し栄養分を生成するオートファギーを介して早期の腫瘍の成長を促します
腫瘍の微小環境における自殺は腫瘍の進行に不可欠です
オートファギーをターゲットにすることでがん治療の有望な治療法が生まれます

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