Full-length cytokeratin-19 is released by human tumor cells: a potential role in metastatic progression of breast cancer.
Full-length cytokeratin-19 is released by human tumor cells: a potential role in metastatic progression of breast cancer.
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DOI：
10.1186/bcr2326
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Pantel K
中科院分区：
文献类型：
--
作者：
Alix-Panabières C;Vendrell JP;Slijper M;Pellé O;Barbotte E;Mercier G;Jacot W;Fabbro M;Pantel K
我们评估了上皮细胞的主要细胞骨架蛋白之一CK 19是否作为全长蛋白从活的肿瘤细胞中释放，以及这种特性是否与乳腺癌患者的转移进展相关。进行EPISPOT（EPithelial ImmunoSPOT）测定以分析各种来源的癌细胞释放的全长CK 19，并且用质谱分析CK 19的序列。用放线菌酮、布雷菲德菌素A或长春新碱进行额外的功能实验以分析CK 19释放的生物学。CK 19-EPISPOT用于检测45例乳腺癌患者骨髓（BM）中的播散性肿瘤细胞，然后对这些患者进行中位6年的随访。结肠直肠癌细胞系（HT-29、HCT 116、Caco-2）和乳腺癌细胞系（MCF-7、SKBR 3和MDA-MB-231）表达并释放CK 19。CK 19-EPISPOT比CK 19-ELISA敏感。具有针对不同CK 19表位的抗体的双重荧光EPISPOT显示全长CK 19的释放，这通过质谱法证实。功能实验表明，CK 19的释放是一个积极的过程，而不仅仅是细胞死亡的结果。CK 19释放细胞（RC）在44%至70%的乳腺癌患者的BM中可检测到。这种发生率和CK 19-RC的数量与明显转移的存在相关，与没有这些细胞的患者相比，CK 19-RC患者的生存率降低（P = 0.025，对数秩检验; P = 0.0019，风险比，4.7;多变量分析）。全长CK 19由活的上皮肿瘤细胞释放，并且CK 19-RC可能构成具有高转移特性的乳腺癌细胞的生物活性亚群。
We evaluated whether CK19, one of the main cytoskeleton proteins of epithelial cells, is released as full-length protein from viable tumor cells and whether this property is relevant for metastatic progression in breast cancer patients. EPISPOT (EPithelial ImmunoSPOT) assays were performed to analyze the release of full-length CK19 by carcinoma cells of various origins, and the sequence of CK19 was analyzed with mass spectrometry. Additional functional experiments with cycloheximide, Brefeldin A, or vincristine were done to analyze the biology of the CK19-release. CK19-EPISPOT was used to detect disseminated tumor cells in bone marrow (BM) of 45 breast cancer patients who were then followed up over a median of 6 years. CK19 was expressed and released by colorectal (HT-29, HCT116, Caco-2) and breast (MCF-7, SKBR3, and MDA-MB-231) cancer cell lines. The CK19-EPISPOT was more sensitive than the CK19-ELISA. Dual fluorescent EPISPOT with antibodies against different CK19 epitopes showed the release of the full-length CK19, which was confirmed by mass spectrometry. Functional experiments indicated that CK19 release was an active process and not simply the consequence of cell death. CK19-releasing cells (RCs) were detectable in BM of 44% to 70% of breast cancer patients. This incidence and the number of CK19-RCs were correlated to the presence of overt metastases, and patients with CK19-RCs had a reduced survival as compared with patients without these cells (P = 0.025, log-rank test; P = 0.0019, hazard ratio, 4.7; multivariate analysis). Full-length CK19 is released by viable epithelial tumor cells, and CK19-RCs might constitute a biologically active subset of breast cancer cells with high metastatic properties.
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影响因子：
10.5
作者：
Gudjonsson, T;Villadsen, R;Petersen, OW
通讯作者：
Petersen, OW
影响因子：
64.8
作者：
Kim, S;Wong, P;Coulombe, PA
通讯作者：
Coulombe, PA
影响因子：
2.2
作者：
CZERKINSKY, CC;NILSSON, LA;TARKOWSKI, A
通讯作者：
TARKOWSKI, A
DOI：
10.1007/978-1-59745-398-1_7
发表时间：
2008-01-01
期刊：
FUNCTIONAL PROTEOMICS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Hegmans, Joost P. J. J.;Gerber, Peter J.;Lambrecht, Bart N.
通讯作者：
Lambrecht, Bart N.
影响因子：
9.3
作者：
Alix-Panabières, C;Rebillard, X;Vendrell, JP
通讯作者：
Vendrell, JP