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Alex M. Mlynarek, MD; Richard L. Balys, MD; Jie Su, MSc; Michael P. Hier, MD, FRCSC; Martin J. Black, MD, FRCSC; Moulay A. Alaoui-Jamali, PhD

Arch Otolaryngol Head Neck Surg. 2007;133(9):910-918.

Objective  To identify potential biomarkers of invasiveness in oral squamous cell carcinoma.

Design  A pilot proteomic study for the identification of secreted and cleaved proteins that can serve as potential biomarkers for head and neck carcinoma invasiveness.

Subjects  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/(c) mice.

Interventions  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.

Results  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.

Conclusions  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.

Author Affiliations: Departments of Otolaryngology–Head and Neck Surgery (Drs Mlynarek, Balys, Hier, and Black) and Oncology and Medicine (Mr Su and Dr Alaoui-Jamali), McGill University, and Lady Davis Institute for Medical Research, Segal Comprehensive Cancer Center of the Sir Mortimer B. Davis Jewish General Hospital (Mr Su and Dr Alaoui-Jamali), Montreal, Quebec, Canada.

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