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. Immunohistochemical
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