Mlynarek Alex M, Balys Richard L, Su Jie, Hier Michael P, Black Martin J, Alaoui-Jamali Moulay A
Lady Davis Institute for Medical Research, Segal Comprehensive Cancer Center, 3755 Chemin Côte Ste-Catherine, Montréal, Quebec, Canada.
Arch Otolaryngol Head Neck Surg. 2007 Sep;133(9):910-8. doi: 10.1001/archotol.133.9.910.
To identify potential biomarkers of invasiveness in oral squamous cell carcinoma.
A pilot proteomic study for the identification of secreted and cleaved proteins that can serve as potential biomarkers for head and neck carcinoma invasiveness.
Two primary cell lines and their variants were established from 2 oral squamous cell carcinoma human tissue samples with distinct invasive phenotypes. The cell lines were confirmed to maintain the invasive capacity of the original cancer when implanted into the tongues of immunocompromised RAG-2/gamma(c) mice.
Invasiveness was assessed by the capacity of cells to invade through a matrigel matrix using the Boyden chamber assay and correlated with the invasiveness seen clinically and histologically in patients. In parallel, cell lines were grown in serum-free conditioned medium, which was then used to identify secreted and/or cleaved proteins that emanate from cancer cells, using 2-dimensional gel electrophoresis and matrix-assisted laser desorption-ionization combined with tandem mass spectrometry.
The invasion assays revealed a correlation between cell migration capacity through matrigel matrix and the aggressive phenotype seen in the clinical and histopathological assessments. More than 50 proteins were identified as being differentially secreted in media between the least and the more aggressive cell lines (P < .05). These include proteins that regulate cell metabolism, cell structure, cell adhesion, and cell motility, as well as proteins with undefined function.
We report a sensitive and clinically relevant approach to screen for secreted biomarkers of oral squamous cell carcinoma invasiveness using proteomic technology. Both high- and low-abundant secreted proteins were identified and can represent potential biomarkers for oral cancer.
鉴定口腔鳞状细胞癌侵袭性的潜在生物标志物。
一项探索性蛋白质组学研究，旨在鉴定可作为头颈部癌侵袭性潜在生物标志物的分泌蛋白和裂解蛋白。
从2例具有不同侵袭表型的口腔鳞状细胞癌人体组织样本中建立了两种原代细胞系及其变体。当将这些细胞系植入免疫缺陷的RAG-2/γ(c)小鼠的舌部时，证实它们保持了原发癌的侵袭能力。
使用Boyden小室分析法通过细胞穿过基质胶基质的能力评估侵袭性，并将其与患者临床和组织学上观察到的侵袭性相关联。同时，将细胞系在无血清条件培养基中培养，然后使用二维凝胶电泳和基质辅助激光解吸电离结合串联质谱法来鉴定癌细胞分泌和/或裂解的蛋白质。
侵袭试验揭示了细胞穿过基质胶基质的迁移能力与临床和组织病理学评估中所见的侵袭性表型之间的相关性。在侵袭性最低和最高的细胞系之间的培养基中，鉴定出50多种差异分泌的蛋白质（P <.05）。这些蛋白质包括调节细胞代谢、细胞结构、细胞黏附、细胞运动的蛋白质，以及功能未明的蛋白质。
我们报告了一种使用蛋白质组学技术筛选口腔鳞状细胞癌侵袭性分泌生物标志物的灵敏且与临床相关的方法。已鉴定出高丰度和低丰度的分泌蛋白，它们可能代表口腔癌的潜在生物标志物。
