Lecture4_Vasculatures_Nov.7___2012要素.pdf

Angiogenesis and its Function in Human Disease Yongzhang Luo Cancer Biology Laboratory Beijing Key Laboratory of Protein Therapeutics National Engineering Laboratory for Anti-Tumor Protein Therapeutics Vascular Remodeling Pre-metastasis The integrity of blood vessel is maintained by tunica Tunica: 膜 外膜 Intima: 内膜 Lamina: 薄层 Adventitia: 外膜，动脉外膜 内膜 有弹性的内薄层 有弹性的外薄层 平滑肌细胞 Schematic illustration of blood vessel Vascular remodeling Pre-metastasis The influence of primary tumor on the remodeling of the local vasculature Pericytes Anti-angiogenic Therapy Bergers G, Hanahan D. Nat Rev Cancer 8, 592 (2008) Signaling pathways in vascular maturation PDGF-BB signaling in vascular remodeling Song et al., Cancer Research (2009) PDGF/PDGFR chemotaxis is disrupted in PDGF-BB-overexpressing tumor Song et al., Cancer Research (2009) Screening the potential chemotatic factor(s) PDGF-BB: - + VEGF-A SDF-1 PlGF ANGT2 TGFβ HGF Song et al., Cancer Research (2009) PDGF-BB induces SDF-1 expression in tumor-associated endothelial cells Song et al., Cancer Research (2009) SDF-1 expression is HIF-1α dependent Song et al., Cancer Research (2009) PDGF-BB mediates SDF-1 expression via the PI3K/Akt/mTOR pathway