Pancreatic stellate cells regulate blood vessel density in the stroma of pancreatic ductal adenocarcinoma.
Pancreatic stellate cells regulate blood vessel density in the stroma of pancreatic ductal adenocarcinoma.
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DOI：
10.1016/j.pan.2016.05.393
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发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
Kocher HM
中科院分区：
文献类型：
--
作者：
Di Maggio F;Arumugam P;Delvecchio FR;Batista S;Lechertier T;Hodivala-Dilke K;Kocher HM
胰腺导管腺癌（PDAC）的血管异质性从未被描述过。我们分析了人PDAC的不均匀血管密度沿着其预后相关性。在CD31染色后以自动化方式（Ariol™）分析具有不同胰胆病理的87名患者的组织微阵列，以评估肿瘤旁和泛基质区室中的血管密度。进行体外和离体测定以评估PSC的作用。与胆管癌相比，PDAC具有不同的血管密度和血管分布。PDAC肿瘤旁间质血管少，与泛间质室相比，正常相邻边缘血管丰富。这些特征对患者预后产生不利影响，提示时空PDAC演变的模型。小鼠主动脉环和3D器官型培养物分别显示了来自活化PSC和癌细胞的促血管生成信号和抗血管生成信号。ATRA诱导的静止抑制PSC的促血管生成活性。人PDAC在微观水平上具有可变的血管分布，这表明新的基质定向治疗需要通过病理特征来确定。
The vascular heterogeneity of pancreatic ductal adenocarcinoma (PDAC) has never been characterised. We analysed the heterogeneous vascular density of human PDAC along with its prognostic correlation. Tissue Microarrays of 87 patients with different pancreatico-biliary pathologies were analysed in an automated manner (Ariol™) after CD31 staining to assess vascular density in juxta-tumoral and panstromal compartments. In vitro and ex vivo assays were carried out to assess the role of PSC. PDAC has a distinct vascular density and distribution of vessels compared to cholangiocarcinoma. The PDAC juxta-tumoral stroma was hypovascular and the normal adjacent rim was hypervascular compared to the panstromal compartment. These features adversely affected patient prognosis, suggesting a model for spatio-temporal PDAC evolution. Mice aortic rings and 3D organotypic cultures demonstrated pro- and anti-angiogenic signalling from activated PSC and cancer cells respectively. ATRA-induced quiescence suppressed the pro-angiogenic activity of PSC. Human PDAC has variable vascularity at microscopic level suggesting that novel stromal directed therapies would need to be determined by pathological characteristics.
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影响因子：
50.3
作者：
Özdemir BC;Pentcheva-Hoang T;Carstens JL;Zheng X;Wu CC;Simpson TR;Laklai H;Sugimoto H;Kahlert C;Novitskiy SV;De Jesus-Acosta A;Sharma P;Heidari P;Mahmood U;Chin L;Moses HL;Weaver VM;Maitra A;Allison JP;LeBleu VS;Kalluri R
通讯作者：
Kalluri R
影响因子：
29.4
作者：
Froeling, Fieke E. M.;Feig, Christine;Kocher, Hemant M.
通讯作者：
Kocher, Hemant M.
影响因子：
29.4
作者：
Ene-Obong A;Clear AJ;Watt J;Wang J;Fatah R;Riches JC;Marshall JF;Chin-Aleong J;Chelala C;Gribben JG;Ramsay AG;Kocher HM
通讯作者：
Kocher HM
影响因子：
11.1
作者：
Coleman, Stacey J.;Chioni, Athina-Myrto;Ghallab, Mohammed;Anderson, Rhys K.;Lemoine, Nicholas R.;Kocher, Hemant M.;Grose, Richard P.
通讯作者：
Grose, Richard P.
影响因子：
29.4
作者：
Bachem, MG;Sch端nemann, M;Adler, G
通讯作者：
Adler, G