Plexin-B2は血管新生の生理学的および病理学的機能を媒介する
Wenhao Yu1, Kevin A Goncalves2, Shuping Li1
1Molecular Oncology Research Institute, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA; Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Cell
|November 4, 2017
まとめ
プラキシンB2 (PLXNB2) は,細胞表面受容体として血管新生素 (ANG) の作用を介し,細胞の成長と再生に作用する. この相互作用をターゲットにすることで,癌や神経変性疾患の治療の可能性が示されています.
科学分野:
- 生物化学
- 細胞生物学
- 分子医学
背景:
- 血管新生素 (ANG) は,細胞の成長,生存,再生に関与するリボヌクレアース (RNase) である.
- ANGは,その機能のために受容体媒介の内細胞化を必要とするが,その細胞表面受容体は以前は特定されなかった.
研究 の 目的:
- 血管新生素 (ANG) の機能的細胞表面受容体を特定する.
- ANG媒介細胞プロセスにおけるこの受容体の役割を調査する.
- ANG受容体相互作用を標的とした治療の可能性を評価する.
主な方法:
- 様々な細胞タイプ (内皮細胞,がん細胞,神経細胞,造血幹細胞および祖先細胞) を用いた機能検査.
- ANG受容体としてのプレキシン-B2 (PLXNB2) の識別
- PLXNB2のANG結合部位に対する抗体を用いたin vitroおよびin vivo試験
主要な成果:
- 複数の細胞タイプにおけるANGの機能的受容体として,プレキシン-B2 (PLXNB2) が特定されました.
- PLXNB2は細胞内RNA処理を媒介し,細胞の成長,生存,再生に対するANGの効果に貢献する.
- PLXNB2- ANGの相互作用を標的とした抗体は腫瘍の成長を抑制し,神経保護を促進し,白血病の進行を減少させた.
結論:
- PLXNB2は,ANGの生理学的および病理学的機能に不可欠です.
- PLXNB2-ANGの相互作用を標的とした治療は,固体および造血性がんの治療に有望である.
- PLXNB2-ANG経路は,神経変性疾患の潜在的治療標的である.
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