Elevated expression of stromal palladin predicts poor clinical outcome in renal cell carcinoma.
Elevated expression of stromal palladin predicts poor clinical outcome in renal cell carcinoma.
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DOI：
10.1371/journal.pone.0021494
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Cukierman E
中科院分区：
文献类型：
--
作者：
Gupta V;Bassi DE;Simons JD;Devarajan K;Al-Saleem T;Uzzo RG;Cukierman E
间质肾细胞癌（RCC）在支持肿瘤进展中的作用尚不清楚。在这里，我们试图确定几种基质活化标志物对患者生存的预测价值，以及基于成纤维细胞来源的细胞外基质（ECM）的三维（3D）培养的可行性，该培养来源于临床标本，以重现体外基质行为。使用注释良好的肿瘤微阵列评估所选基质标志物的临床相关性，其中评估基质标志物表达水平并与患者结果进行比较。此外，采用来源于从患者匹配的正常肾脏、原发性RCC和转移性肿瘤收获的成纤维细胞的体外3D系统来评估已知基质标志物的水平和定位，所述基质标志物例如肌动蛋白结合蛋白帕拉丁、α-平滑肌肌动蛋白（α-SMA）、纤连蛋白及其剪接形式EDA。结果表明，RCC表现出高水平的间质palladin与预后不良相关，如总生存时间所示。相反，间质中palladin表达水平低的RCC病例表明生存时间延长，因此结局更好。成纤维细胞衍生的3D培养物有助于将基质RCC分类为离散的进行性基质阶段，还显示α-SMA和palladin的表达水平和应力纤维定位增加，以及纤连蛋白及其剪接变体EDA的地形组织。这些观察结果与这些标志物在体内的表达水平一致。该研究提出，palladin构成了非转移性RCC预后不良的有用标志物，而体外3D培养准确地代表了特定患者的肿瘤相关基质室。我们的观察结果支持这样的信念，即基质palladin评估具有临床相关性，从而验证了使用这些3D培养来研究进行性RCC相关基质和影响肿瘤发生的基质依赖性机制。评价肾细胞癌间质活化的临床价值值得进一步研究。
The role that stromal renal cell carcinoma (RCC) plays in support of tumor progression is unclear. Here we sought to determine the predictive value on patient survival of several markers of stromal activation and the feasibility of a fibroblast-derived extracellular matrix (ECM) based three-dimensional (3D) culture stemming from clinical specimens to recapitulate stromal behavior in vitro. The clinical relevance of selected stromal markers was assessed using a well annotated tumor microarray where stromal-marker levels of expression were evaluated and compared to patient outcomes. Also, an in vitro 3D system derived from fibroblasts harvested from patient matched normal kidney, primary RCC and metastatic tumors was employed to evaluate levels and localizations of known stromal markers such as the actin binding proteins palladin, alpha-smooth muscle actin (α-SMA), fibronectin and its spliced form EDA. Results suggested that RCCs exhibiting high levels of stromal palladin correlate with a poor prognosis, as demonstrated by overall survival time. Conversely, cases of RCCs where stroma presents low levels of palladin expression indicate increased survival times and, hence, better outcomes. Fibroblast-derived 3D cultures, which facilitate the categorization of stromal RCCs into discrete progressive stromal stages, also show increased levels of expression and stress fiber localization of α-SMA and palladin, as well as topographical organization of fibronectin and its splice variant EDA. These observations are concordant with expression levels of these markers in vivo. The study proposes that palladin constitutes a useful marker of poor prognosis in non-metastatic RCCs, while in vitro 3D cultures accurately represent the specific patient's tumor-associated stromal compartment. Our observations support the belief that stromal palladin assessments have clinical relevance thus validating the use of these 3D cultures to study both progressive RCC-associated stroma and stroma-dependent mechanisms affecting tumorigenesis. The clinical value of assessing RCC stromal activation merits further study.
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影响因子：
8
作者：
Goicoechea, S. M.;Bednarski, B.;Garcia-Mata, R.;Prentice-Dunn, H.;Kim, H. J.;Otey, C. A.
通讯作者：
Otey, C. A.
DOI：
10.1007/978-1-59745-413-1_19
发表时间：
2009
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Castello-Cros, Remedios;Cukierman, Edna
通讯作者：
Cukierman, Edna
影响因子：
56.9
作者：
Cukierman, E;Pankov, R;Yamada, KM
通讯作者：
Yamada, KM
影响因子：
0.7
作者：
Desmoulière, A;Guyot, C;Gabbiani, C
通讯作者：
Gabbiani, C
影响因子：
7.5
作者：
Council, Leona;Hameed, Omar
通讯作者：
Hameed, Omar