Overexpression of COL11A1 by cancer-associated fibroblasts: clinical relevance of a stromal marker in pancreatic cancer.
Overexpression of COL11A1 by cancer-associated fibroblasts: clinical relevance of a stromal marker in pancreatic cancer.
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与癌症相关的成纤维细胞对COL11A1的过表达：胰腺癌中基质标记的临床相关性。
DOI：
10.1371/journal.pone.0078327
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Barneo L
中科院分区：
文献类型：
--
作者：
García-Pravia C;Galván JA;Gutiérrez-Corral N;Solar-García L;García-Pérez E;García-Ocaña M;Del Amo-Iribarren J;Menéndez-Rodríguez P;García-García J;de Los Toyos JR;Simón-Buela L;Barneo L
胶原蛋白 11A1 (COL11A1) 基因在胰腺癌中过度表达。 COL11A1 蛋白的表达可能参与胰腺癌的促纤维增生事件，但目前还没有特异性染色 COL11A1 蛋白的抗体。总共研究了 54 例胰腺导管腺癌 (PDAC)、23 例慢性胰腺炎 (CP) 样本以及培养的 PDAC 瘤周基质细胞（第 3-6 代）。正常人胰腺组织样本是通过尸体器官捐赠计划获得的。 1) 通过 q-RT-PCR 验证 COL11A1 基因过表达。结果：与正常和 CP 样本相比，PDAC 样本中 COL11A1 基因的表达显着增加。 2) 使用高度特异性的抗 proCOL11A1 抗体通过免疫组织化学分析 COL11A1。结果：抗 proCOL11A1 对 PDAC 的基质细胞/癌症相关成纤维细胞 (CAF) 进行染色，但不会对慢性良性疾病（慢性胰腺炎）基质细胞、上皮细胞或正常成纤维细胞进行染色。 3)抗体辨别能力的评价。结果：抗 proCOL11A1 免疫染色可准确区分 PDAC 和 CP（AUC 0.936，95% CI 0.851，0.981）。 4) 在胰腺组织样本和培养的瘤周胰腺癌基质细胞上与间充质、上皮和星状细胞标记物共染色的 proCOL11A1+ 基质细胞的表型特征。结果：ProCOL11A1+ 细胞呈现不同比例的间充质、星状和上皮标记物（EMT 表型）共染色。使用这种新开发的抗体通过免疫染色检测 proCOL11A1，可以高度准确地区分 PDAC 和 CP。与其他常用于检测 CAF 的抗体不同，抗 proCOL11A1 在正常胰腺的基质细胞中呈阴性，并且在良性炎症中几乎不存在。这些结果强烈表明，proCOL11A1 是 CAF 的特异性标记物，因此，抗 proCOL11A1 是癌症研究和临床诊断的强大新工具。
The collagen11A1 (COL11A1) gene is overexpressed in pancreatic cancer. The expression of COL11A1 protein could be involved in desmoplastic events in pancreatic cancer, but an antibody that specifically stains the COL11A1 protein is not currently available. A total of 54 pancreatic ductal adenocarcinomas (PDAC), 23 chronic pancreatitis (CP) samples, and cultured peritumoral stromal cells of PDAC (passages 3-6) were studied. Normal human pancreas tissue samples were obtained through a cadaveric organ donation program. 1) Validation of COL11A1 gene overexpression by q-RT-PCR. Findings: the expression of COL11A1 gene is significantly increased in PDAC samples vs. normal and CP samples. 2) Analysis of COL11A1 by immunohistochemistry using highly specific anti-proCOL11A1 antibodies. Findings: anti-proCOL11A1 stains stromal cells/cancer-associated fibroblasts (CAFs) of PDAC but it does not stain chronic benign condition (chronic pancreatitis) stromal cells, epithelial cells, or normal fibroblasts. 3) Evaluation of the discrimination ability of the antibody. Findings: anti-proCOL11A1 immunostaining accurately discriminates between PDAC and CP (AUC 0.936, 95% CI 0.851, 0.981). 4) Phenotypic characterization of proCOL11A1+ stromal cells co-staining with mesenchymal, epithelial and stellate cell markers on pancreatic tissue samples and cultured peritumoral pancreatic cancer stromal cells. Findings: ProCOL11A1+ cells present co-staining with mesenchymal, stellate and epithelial markers (EMT phenotype) in different proportions. Detection of proCOL11A1 through immunostaining with this newly-developed antibody allows for a highly accurate distinction between PDAC and CP. Unlike other available antibodies commonly used to detect CAFs, anti-proCOL11A1 is negative in stromal cells of the normal pancreas and almost absent in benign inflammation. These results strongly suggest that proCOL11A1 is a specific marker for CAFs, and thus, anti-proCOL11A1 is a powerful new tool for cancer research and clinical diagnostics.
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影响因子：
0.7
作者：
Desmoulière, A;Guyot, C;Gabbiani, C
通讯作者：
Gabbiani, C
影响因子：
3.8
作者：
Fischer, H;Salahshor, S;Lindblom, A
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11.2
作者：
Hwang, Rosa F.;Moore, Todd;Logsdon, Craig D.
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Logsdon, Craig D.
影响因子：
4.8
作者：
Grützmann, R;Pilarsky, C;Saeger, HD
通讯作者：
Saeger, HD
影响因子：
2.9
作者：
IMAMURA, T;IGUCHI, H;IMAMURA, M
通讯作者：
IMAMURA, M