GDNF secreted from adipose-derived stem cells stimulates VEGF-independent angiogenesis.
GDNF secreted from adipose-derived stem cells stimulates VEGF-independent angiogenesis.
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脂肪干细胞分泌的 GDNF 刺激不依赖 VEGF 的血管生成
DOI：
10.18632/oncotarget.9208
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发表时间：
2016-06-14
期刊：
影响因子：
--
通讯作者：
Du Y
中科院分区：
文献类型：
--
作者：
Zhong Z;Gu H;Peng J;Wang W;Johnstone BH;March KL;Farlow MR;Du Y
脂肪组织间质含有大量间充质干细胞（MSC），促进新血管的形成和稳定。这些脂肪来源的干细胞（ASC）在体外促进血管结构的新生形成。我们研究了ASC分泌的血管生成因子，发现胶质源性神经营养因子（GDNF）是内皮细胞网络形成的关键介质。研究发现，单独使用GDNF或存在于asc条件培养基（ASC-CM）均可刺激人脐静脉内皮细胞（HUVECs）形成毛细血管网络，且这种作用完全独立于血管内皮生长因子（VEGF）活性。此外，我们发现GDNF刺激毛细血管网络形成，而不是VEGF，可以被Ret（在转染过程中重排）受体拮抗剂RPI-1 （GDNF信号抑制剂）阻断。此外，GDNF被发现在对VEGF抗体抗血管生成治疗有抵抗力的癌细胞中过度表达。肝细胞癌（HCC）是一种非神经相关的癌症，与正常肝细胞相比，肝癌细胞中的GDNF高度过表达。我们的数据强烈提示，除了VEGF外，ASC和HCC细胞分泌的GDNF可能是促进病理性新生血管形成的另一个重要因素。因此，GDNF可能是HCC和肥胖治疗的潜在治疗靶点。
Adipose tissue stroma contains a population of mesenchymal stem cells (MSC) promote new blood vessel formation and stabilization. These adipose-derived stem cells (ASC) promote de novo formation of vascular structures in vitro. We investigated the angiogenic factors secreted by ASC and discovered that glial-derived neurotrophic factor (GDNF) is a key mediator for endothelial cell network formation. It was found that both GDNF alone or present in ASC-conditioned medium (ASC-CM) stimulated capillary network formation by using human umbilical vein endothelial cells (HUVECs) and such an effect was totally independent of vascular endothelial growth factor (VEGF) activity. Additionally, we showed stimulation of capillary network formation by GDNF, but not VEGF, could be blocked by the Ret (rearranged during transfection) receptor antagonist RPI-1, a GDNF signaling inhibitor. Furthermore, GDNF were found to be overexpressed in cancer cells that were resistant to the anti-angiogenic treatment using the VEGF antibody. Cancer cells in the liver hepatocellular carcinoma (HCC), a non-nervous related cancer, highly overexpressed GDNF as compared to normal liver cells. Our data strongly suggest that, in addition to VEGF, GDNF secreted by ASC and HCC cells, may be another important factor promoting pathological neovascularization. Thus, GDNF may be a potential therapeutic target for HCC and obesity treatments.
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DOI：
10.1158/1078-0432.ccr-11-1916
发表时间：
2012-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
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120.1
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影响因子：
5.7
作者：
Chen, Jing;Wang, Jieqiong;Liu, Mingyao
通讯作者：
Liu, Mingyao
影响因子：
4
作者：
Ballas MS;Chachoua A
通讯作者：
Chachoua A
影响因子：
4.1
作者：
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Somanath, Payaningal R.