PDGF-C induces maturation of blood vessels in a model of glioblastoma and attenuates the response to anti-VEGF treatment.
PDGF-C induces maturation of blood vessels in a model of glioblastoma and attenuates the response to anti-VEGF treatment.
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PDGF-C在胶质母细胞瘤模型中诱导血管成熟，并减弱对抗VEGF治疗的反应。
DOI：
10.1371/journal.pone.0005123
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Jain RK
中科院分区：
文献类型：
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作者：
di Tomaso E;London N;Fuja D;Logie J;Tyrrell JA;Kamoun W;Munn LL;Jain RK
最近的临床试验显示VEGF抑制剂在治疗复发性胶质母细胞瘤（GBM）方面有希望。然而，由于肿瘤逃避抗vegf治疗，生存获益通常是短暂的。在这里，我们检验了血小板衍生生长因子- c (PDGF- c)， PDGF家族的一种异构体，独立于VEGF途径影响GBM进展并阻碍抗VEGF治疗的假设。我们首先发现PDGF-C存在于人类GBMs中。然后，我们在人GBM细胞系U87MG中过表达或下调PDGF-C，并在裸鼠颅窗中培养它们，使用活体显微镜评估血管结构和功能。与亲代或sirna转染的肿瘤相比，PDGF-C过表达的肿瘤血管直径更小，血管通透性更低。此外，与对照组相比，PDGF-C过表达肿瘤的血管中NG2阳性血管周围细胞的覆盖范围更广，IV型胶原基膜更厚。用抗vegfr -2抗体DC101治疗，诱导亲代肿瘤血管密度降低，但对PDGF-C过表达的肿瘤没有影响。这些结果表明PDGF-C在胶质瘤血管成熟和稳定中起着重要作用，并且它可以减弱抗vegf治疗的反应，可能有助于逃离血管正常化。
Recent clinical trials of VEGF inhibitors have shown promise in the treatment of recurrent glioblastomas (GBM). However, the survival benefit is usually short-lived as tumors escape anti-VEGF therapies. Here we tested the hypothesis that Platelet Derived Growth Factor-C (PDGF-C), an isoform of the PDGF family, affects GBM progression independent of VEGF pathway and hinders anti-VEGF therapy. We first showed that PDGF-C is present in human GBMs. Then, we overexpressed or downregulated PDGF-C in a human GBM cell line, U87MG, and grew them in cranial windows in nude mice to assess vessel structure and function using intravital microscopy. PDGF-C overexpressing tumors had smaller vessel diameters and lower vascular permeability compared to the parental or siRNA-transfected tumors. Furthermore, vessels in PDGF-C overexpressing tumors had more extensive coverage with NG2 positive perivascular cells and a thicker collagen IV basement membrane than the controls. Treatment with DC101, an anti-VEGFR-2 antibody, induced decreases in vessel density in the parental tumors, but had no effect on the PDGF-C overexpressing tumors. These results suggest that PDGF-C plays an important role in glioma vessel maturation and stabilization, and that it can attenuate the response to anti-VEGF therapy, potentially contributing to escape from vascular normalization.
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影响因子：
11.2
作者：
Anderberg C;Li H;Fredriksson L;Andrae J;Betsholtz C;Li X;Eriksson U;Pietras K
通讯作者：
Pietras K
影响因子：
10.5
作者：
Dai, C;Celestino, JC;Holland, EC
通讯作者：
Holland, EC
影响因子：
2.9
作者：
Campbell, Jean S.;Johnson, Melissa M.;Fausto, Nelson
通讯作者：
Fausto, Nelson
影响因子：
21.3
作者：
Bergsten, E;Uutela, M;Eriksson, U
通讯作者：
Eriksson, U
DOI：
10.1038/nrc2442
发表时间：
2008-08
期刊：
Nature reviews. Cancer
影响因子：
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作者：
通讯作者：
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