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グライカンCA19-9はマウスにおける炎と臓がんを誘発する
Dannielle D Engle1,2, Hervé Tiriac1,2, Keith D Rivera1
1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Science (New York, N.Y.)
|June 22, 2019
まとめ
変化したグリコシレーション,特にシアリル・ルイスa (CA19- 9) は,EGFRのシグナル伝達を活性化することで,マウスで重度の炎と臓がんを引き起こします. CA19-9によって引き起こされるこの炎は逆行性であり,潜在的な治療目標です.
科学分野:
- 生物化学
- 分子生物学
- 腫瘍学
背景:
- グライコシレーションの変化は炎症と癌に関連しています.
- 病気の病原性における特定のグリカン変化の役割は不明である.
研究 の 目的:
- 臓疾患の病原性におけるシアリル・ルイスa (CA19-9) の役割を調査する.
- CA19-9を炎と臓がんの潜在的治療標的として検討する.
主な方法:
- マウスにおけるフコシルトランスフェラーゼ3とβ1,3-ガラクソシルトランスフェラーゼ5の誘導表現により,CA19-9を分解する.
- 皮質成長因子受容体 (EGFR) のシグナル伝達に対するCA19-9の効果のメカニズムを調査した.
- 抗体阻害とフィブリン3とEGFRを標的とした治療法
主要な成果:
- CA19 - 9発現はEGFR過活性化による急速な重度の炎を誘発した.
- ファイブリン3のCA19-9改変によりEGFRとの相互作用が強化された.
- EGFR リガンドであるフィブリン3またはCA19-9の阻害により,EGFRの過剰活性化が防止されました.
- CA19-9誘発性炎は逆行し,CA19-9抗体で治療することができました.
- CA19-9はKrasと協力して 積極的な臓がんを誘発した
結論:
- CA19-9は,炎と臓がんの病因において重要な役割を果たします.
- CA19-9は,臓疾患の潜在的な治療標的である.
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