化学抵抗性ニッチのDNA損傷による誘導

Luke A Gilbert¹, Michael T Hemann

¹The Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, 02139, USA.

Cell

|October 30, 2010

まとめ

化学療法は,IL-6の放出のような腫瘍のマイクロ環境反応を誘発し,リンパ腫細胞を保護します. これにより,化学療法に抵抗するニッチが形成され,残留疾患の最小化と潜在的再発を促進します.

科学分野:

腫瘍学腫瘍学
免疫学免疫学とは
細胞生物学細胞生物学

背景:

細胞内在のメカニズムは,化学療法への反応に大きな影響を与えます.
治療結果における腫瘍の微環境の役割は,まだ十分に理解されていない.

研究の目的:

遺伝子毒性化学療法後のリンパ腫細胞生存に腫瘍の微環境がどのように影響するか調査する.
化学抵抗を与えるマイクロ環境内の特定の要因を特定する.

主な方法:

Burkittのリンパ腫のマウスモデルを使用しました.
治療効果の評価のために遺伝子毒性化学療法を受けた.
腫瘍の微小環境におけるパラクリン因子放出と細胞反応を分析した.

主要な成果:

パラクリン系因子,特にインターリューキン-6 (IL-6) とメタロプロテインゼ-1 (Timp-1) の組織阻害剤は,DNA損傷後のチムスで放出されました.
これらの要因は,最小限の残留腫瘍細胞をサポートする"化学療法に抵抗するニッチ"を作成しました.
p38のシグナル伝達に依存する胸膜内皮細胞からの急性IL-6の放出は,ストロマル細胞老化に先行した.

結論:

遺伝子毒性化学療法は,腫瘍の回帰を誘発しますが,また,保護的マイクロ環境ストレス反応を活性化します.
これらの反応は,特定の場所にある腫瘍細胞のサブセットをシールドし,再発の可能性に貢献します.
マイクロ環境の相互作用をターゲットにすることは,化学療法の有効性を改善するために非常に重要です.

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