Gene-expression profiling of microdissected breast cancer microvasculature identifies distinct tumor vascular subtypes.
Gene-expression profiling of microdissected breast cancer microvasculature identifies distinct tumor vascular subtypes.
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DOI：
10.1186/bcr3246
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发表时间：
2012-08-20
期刊：
影响因子：
--
通讯作者：
Park M
中科院分区：
文献类型：
--
作者：
Pepin F;Bertos N;Laferrière J;Sadekova S;Souleimanova M;Zhao H;Finak G;Meterissian S;Hallett MT;Park M
Angiogenesis represents a potential therapeutic target in breast cancer. However, responses to targeted antiangiogenic therapies have been reported to vary among patients. This suggests that the tumor vasculature may be heterogeneous and that an appropriate choice of treatment would require an understanding of these differences. To investigate whether and how the breast tumor vasculature varies between individuals, we isolated tumor-associated and matched normal vasculature from 17 breast carcinomas by laser-capture microdissection, and generated gene-expression profiles. Because microvessel density has previously been associated with disease course, tumors with low (n = 9) or high (n = 8) microvessel density were selected for analysis to maximize heterogeneity for this feature. We identified differences between tumor and normal vasculature, and we describe two subtypes present within tumor vasculature. These subtypes exhibit distinct gene-expression signatures that reflect features including hallmarks of vessel maturity. Potential therapeutic targets (MET, ITGAV, and PDGFRβ) are differentially expressed between subtypes. Taking these subtypes into account has allowed us to derive a vascular signature associated with disease outcome. Our results further support a role for tumor microvasculature in determining disease progression. Overall, this study provides a deeper molecular understanding of the heterogeneity existing within the breast tumor vasculature and opens new avenues toward the improved design and targeting of antiangiogenic therapies.
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DOI：
10.1084/jem.20091846
发表时间：
2010-03-15
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Helfrich I;Scheffrahn I;Bartling S;Weis J;von Felbert V;Middleton M;Kato M;Ergün S;Augustin HG;Schadendorf D
通讯作者：
Schadendorf D
影响因子：
4.6
作者：
Houle, Francois;Huot, Jacques
通讯作者：
Huot, Jacques
DOI：
10.1152/ajpheart.01047.2006
发表时间：
2007-03-01
影响因子：
4.8
作者：
Chien, Shu
通讯作者：
Chien, Shu
DOI：
10.1038/nrc2442
发表时间：
2008-08
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
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DOI：
10.1038/nrclinonc.2009.63
发表时间：
2009-06
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
通讯作者：
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