KAI1（CD82）是控制血管生成和将血管生成环境切换到静止状态的关键分子。
KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic milieu to quiescent state.
机构信息
National Research Laboratory for Stem Cell Niche, Center for Medical Innovation, Seoul National University Hospital, Seoul, Republic of Korea.
Center of Cell- and Bio-Therapy (CBT), Seoul National University Hospital, Seoul, Republic of Korea.
出版信息
J Hematol Oncol. 2021 Sep 16;14(1):148. doi: 10.1186/s13045-021-01147-6.
BACKGROUND
Little is known about endogenous inhibitors of angiogenic growth factors. In this study, we identified a novel endogenous anti-angiogenic factor expressed in pericytes and clarified its underlying mechanism and clinical significance.
METHODS
Herein, we found Kai1 knockout mice showed significantly enhanced angiogenesis. Then, we investigated the anti-angiogenic roll of Kai1 in vitro and in vivo.
RESULTS
KAI1 was mainly expressed in pericytes rather than in endothelial cells. It localized at the membrane surface after palmitoylation by zDHHC4 enzyme and induced LIF through the Src/p53 pathway. LIF released from pericytes in turn suppressed angiogenic factors in endothelial cells as well as in pericytes themselves, leading to inhibition of angiogenesis. Interestingly, KAI1 had another mechanism to inhibit angiogenesis: It directly bound to VEGF and PDGF and inhibited activation of their receptors. In the two different in vivo cancer models, KAI1 supplementation significantly inhibited tumor angiogenesis and growth. A peptide derived from the large extracellular loop of KAI1 has been shown to have anti-angiogenic effects to block the progression of breast cancer and retinal neovascularization in vivo.
CONCLUSIONS
KAI1 from PC is a novel molecular regulator that counterbalances the effect of angiogenic factors.
背景
关于血管生成生长因子的内源性抑制剂知之甚少。在这项研究中，我们鉴定了一种新的内源性抗血管生成因子，该因子在周细胞中表达，并阐明了其潜在的机制和临床意义。
方法
在此，我们发现 Kai1 敲除小鼠表现出明显增强的血管生成。然后，我们在体外和体内研究了 Kai1 的抗血管生成作用。
结果
KAI1 主要在周细胞中表达，而不是在血管内皮细胞中表达。它在 zDHHC4 酶的棕榈酰化作用后定位于细胞膜表面，并通过Src/p53 途径诱导 LIF。周细胞释放的 LIF 反过来抑制内皮细胞和周细胞自身中的血管生成因子，从而抑制血管生成。有趣的是，KAI1 具有另一种抑制血管生成的机制：它直接与 VEGF 和 PDGF 结合并抑制其受体的激活。在两种不同的体内癌症模型中，KAI1 的补充显著抑制了肿瘤血管生成和生长。源自 KAI1 大细胞外环的肽已显示出抗血管生成作用，可阻止体内乳腺癌和视网膜新生血管的进展。
结论
PC 中的 KAI1 是一种新的分子调节剂，可平衡血管生成因子的作用。
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