Multiple kallikrein (KLK 5, 7, 8, and 10) expression in squamous cell carcinoma of the oral cavity

Jason R. Pettus¹*, Jeffrey J. Johnson¹*, Zonggao Shi¹, J. Wade Davis², Jennifer Koblinski³, Supurna Ghosh⁴, Yueying Liu¹, Matthew J. Ravosa¹, Shellaine Frazier¹ and M. Sharon Stack¹

Departments of ¹Pathology & Anatomical Sciences and ²Department of Health Management & Informatics and Statistics, University of Missouri School of Medicine, Columbia, ³Pathology and ⁴Surgery, Northwestern University Feinberg School of Medicine, Chicago, USA
*These two authors contributed equally .

Offprint requests to: M. Sharon Stack, Department of Pathology and Anatomical Science, University of Missouri School of Medicine, M214E Medical Sciences Bldg. 1 Hospital Drive, Columbia, MO 65212, USA. e-mail: stackm@missouri.edu


Summary. Oral squamous cell carcinoma (OSCC) represents 3% of all cancer deaths in the U.S. and is ranked one of the top 10 cancers worldwide. The 5-year survival rate has remained at a low 50% for the past several decades, necessitating discovery of novel biomarkers of aggressive disease and therapeutic targets. As overexpression of urinary type plasminogen activator and receptor (uPA/R) in OSCC is associated with malignant progression and poor outcome, cell lines were generated with either overexpression (SCC25-uPAR+) or silencing (SCC25-uPAR-KD) of uPAR. As SCC25-uPAR+ tumors behaved more aggressively both in vitro and in vivo, comparative cDNA microarray analysis was used to identify additional genes that may be associated with aggressive tumors. Four members of the human tissue kallikrein family (KLK 5, 7, 8, and 10) were identified and real-time RT-PCR (qPCR) was used to verify and quantify gene expression. qPCR analysis revealed 2.8-, 5.3-, 4.0-, and 3.5-fold increases in gene expression for KLK5, 7, 8, and 10, respectively, in SCC25-uPAR+ versus SCC25-uPAR-KD. Immuno-histochemical analysis demonstrated strong reactivity for KLKs 5, 7, 8 and 10 in both orthotopic murine tumors and human OSCC tissues. Control experiments show lack of reactivity against KLK3 (prostate specific antigen). These results demonstrate that kallikreins 5, 7, 8, and 10 are abundantly expressed in human OSCC and may be implicated in malignant progression. Histol Histopathol 24, 197-207 (2009)

Key words: Oral cancer, Squamous cell carcinoma, Kallikrein

DOI: 10.14670/HH-24.197