アデノマに関連したバリアデフェクトと微生物産物は,IL-23/IL-17媒介の腫瘍増殖を誘発する

Sergei I Grivennikov¹, Kepeng Wang, Daniel Mucida

¹Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, California 92093-0723, USA.

Nature

|October 5, 2012

まとめ

結腸直腸がんの成長は炎症によって引き起こされます. 腫瘍における遺伝的変化により,微生物の産物が侵入し,炎症性腸疾患はなくとも,腫瘍の進行を促進する炎症を引き起こします.

科学分野:

腫瘍学腫瘍学
免疫学免疫学とは
胃腸内科胃腸内科

背景:

結腸直腸がん (CRC) は,炎症性腸疾患なしに発症することが多いが,炎症性遺伝子シグネチャーを示し,浸透する.
腫瘍に起因する炎症,特にTヘルパーインタールイキン-17 (T(H) 17細胞を含む炎症は,CRCの生存率の低下と関連しています.
CRCにおける腫瘍誘発性炎症を誘発するメカニズムは,未だに十分に理解されていない.

研究の目的:

結腸直腸がんにおける腫瘍誘発の炎症を誘発するメカニズムを調査する.
CRC腫瘍発生におけるインタールイキン-23 (IL-23) とインタールイキン-17 (IL-17) の役割を明らかにする.
CRCの発達に対する上皮膜のバリアの整合性の影響を調査する.

主な方法:

大腸直腸腫瘍発生のマウスモデルを利用した.
炎症シグネチャーやバリアタンパク質を含む遺伝子発現を分析した.
IL-23/IL-17シグナル伝達経路の役割を調査した.
免疫細胞の浸透と活性化を調べました.

主要な成果:

IL-23シグナリングは,CRCの成長,進行,および腫瘍性IL-17応答の発達を著しく促進します.
腫瘍に浸透する微生物製品によって活性化される腫瘍関連骨髄細胞は,IL-23の主要な源である.
障壁タンパク質の欠陥発現は,早期および後期の大腸直腸腫瘍の両方で観察され,微生物の侵入を容易にしました.

結論:

癌を誘発する遺伝病変によって引き起こされる上皮壁の悪化は,微生物製品が腫瘍に侵入することを可能にします.
この侵入は,IL-23とIL-17による腫瘍誘発の炎症を誘発し,その後腫瘍の成長と進行を促します.
これらのメカニズムの理解は,CRCの潜在的な治療目標を提供します.

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