Secretome-Based Identification and Characterization of Potential Biomarkers in Thyroid Cancer

被引：33
|
作者：
Kashat, Lawrence [1 ,2 ,3 ]
So, Anthony K. -C. [1 ,2 ]
Masui, Olena [4 ,5 ]
Wang, X. Simon [4 ,5 ]
Cao, Jun [1 ,2 ]
Meng, Xianwang [1 ,2 ]
MacMillan, Christina
Ailles, Laurie E. [6 ]
Siu, K. W. Michael [4 ,5 ]
Ralhan, Ranju [1 ,2 ,3 ,4 ,5 ,7 ,8 ]
Walfish, Paul G. [1 ,2 ,3 ,7 ,8 ]
机构：
[1] Mt Sinai Hosp, Dept Pathol & Lab Med, Alex & Simona Shnaider Lab Mol Oncol, Toronto, ON M5G 1X5, Canada
[2] Mt Sinai Hosp, Joseph & Mildred Sonstine Family Ctr Head & Neck, Toronto, ON M5G 1X5, Canada
[3] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada
[4] York Univ, Dept Chem, N York, ON M3J 1P3, Canada
[5] York Univ, Ctr Res Mass Spectrometry, N York, ON M3J 1P3, Canada
[6] Ontario Canc Inst, MaRS Ctr, Div Stem Cell & Dev Biol, Toronto, ON M5G 1L7, Canada
[7] Mt Sinai Hosp, Dept Otolaryngol Head & Neck Surg, Toronto, ON M5G 1X5, Canada
[8] Univ Toronto, Dept Otolaryngol Head & Neck Surg, Toronto, ON M5G 2N2, Canada
来源：
JOURNAL OF PROTEOME RESEARCH | 2010年 / 9卷 / 11期
基金：
加拿大健康研究院;
关键词：
proteomics; one-dimensional liquid chromatography-tandem mass spectrometry; secretome; thyroid cancer; biomarkers; secretory proteins; MULTIDIMENSIONAL LIQUID-CHROMATOGRAPHY; FINE-NEEDLE-ASPIRATION; CONDITIONED MEDIA; PLASMINOGEN-ACTIVATOR; PROTHYMOSIN-ALPHA; PROSTATE-CANCER; GENE-EXPRESSION; CELL-LINES; ABSOLUTE QUANTIFICATION; PROTEOMICS ANALYSIS;
D O I：
10.1021/pr100529t
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
In search of thyroid cancer biomarkers, proteins secreted by thyroid cancer cell lines, papillary-derived TPC-1 and anaplastic-derived CAL62, were analyzed using liquid chromatography-tandem mass spectrometry. Of 46 high-confidence identifications, 6 proteins were considered for verification in thyroid cancer patients' tissue and blood. The localization of two proteins, nucleolin and prothymosin-alpha. (PTMA), was confirmed in TPC-1 and CAL62 cells by confocal microscopy and immunohistochemically in xenografts of TPC-1 cells in NOD/SCID/gamma mice and human thyroid cancers (48 tissues). Increased nuclear and cytoplasmic expression of PTMA was observed in anaplastic compared to papillary and poorly differentiated carcinomas. Nuclear expression of nucleolin was observed in all subtypes of thyroid carcinomas, along with faint cytoplasmic expression in anaplastic cancers. Importantly, PTMA, nucleolin, clusterin, cysteine-rich angiogenic inducer 61, enolase 1, and biotinidase were detected in thyroid cancer patients' sera, warranting future analysis to confirm their potential as blood-based thyroid cancer markers. In conclusion, we demonstrated the potential of secretome analysis of thyroid cancer cell lines to identify novel proteins that can be independently verified in cell lines, xenografts, tumor tissues, and blood samples of thyroid cancer patients. These observations support their potential utility as minimally invasive biomarkers for thyroid carcinomas and their application in management of these diseases upon future validation.
引用
收藏
页码：5757 / 5769
页数：13
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