Decreased expression of kallikrein-related peptidase 13: possible contribution to metastasis of human oral cancer.
The human kallikrein-related peptidase family is comprised of 15 serine protease genes on chromosome 19q13.4. Our previous microarray analyses showed that the gene kallikrein-related peptidase 13 (KLK13) was down-regulated in oral squamous cell carcinoma (OSCC) cell lines. We evaluated the expression status of KLK13 in primary OSCCs and performed functional molecular experiments in OSCC cell lines. In 102 primary tumors studied, KLK13 expression significantly (P < 0.05) decreased compared with matched normal counterparts. Interestingly, KLK13-negative cases correlated significantly (P < 0.05) with regional lymph node metastasis. In vitro, cells overexpressing KLK13 (oeKLK13) had decreased invasiveness and motility and up-regulation of adhesion molecules (E-cadherin, α-catenin, β-catenin, junction plakoglobin, plakophilin4, desmocollin2, desmoglein3, and desmoplakin) compared with control cells. A rescue experiment that transfected oeKLK13 cells with siRNA against KLK13 restored invasiveness and migration activities with down-regulated adhesion molecules. Based on our results, we concluded that KLK13 may play an important role in regulating cellular migration and invasiveness, making the loss of KLK13 a potential biomarker for early detection of lymph node metastasis in OSCCs.
Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Shunsaku
S
Ishige
Atsushi
A
Kasamatsu
Kenji
K
Ogoshi
Yasuhiro
Y
Saito
Katsuya
K
Usukura
Hidetaka
H
Yokoe
Yukinao
Y
Kouzu
Hirofumi
H
Koike
Yosuke
Y
Sakamoto
Katsunori
K
Ogawara
Masashi
M
Shiiba
Hideki
H
Tanzawa
Katsuhiro
K
Uzawa
D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D006801:Humans; D007610:Kallikreins / Q000096:biosynthesis* / Q000235:genetics; D008207:Lymphatic Metastasis; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D034741:RNA, Small Interfering; C470778:KLK13 protein, human; D007610:Kallikreins
adhesion molecules; invasiveness; kallikrein-related peptidase 13; migration; oral squamous cell carcinoma