Inhibition of invasion and metastasis in oral cancer by targeting urokinase-type plasminogen activator receptor.
There have been reports of strong correlations between poor prognosis in various cancers and concomitant expression of urokinase-type plasminogen activator (uPA) and its surface receptor (uPAR). We and others have previously shown that the uPA system plays a significant role in a subset of head and neck squamous cell carcinoma. In the present study, we found that uPAR is required for invasion and metastasis of highly malignant oral cancer cells (OSC-19). Treating OSC-19 cells with antisense oligonucleotides (AS) targeting uPAR resulted in a dramatic decrease of uPAR mRNA expression. Furthermore, pretreatment with AS or siRNA targeting uPAR inhibited progression of OSC-19 cells in experimental models. These results suggest that overexpression of uPAR increases the invasiveness and metastasis of OSC-19 cells, and that uPAR is a promising therapeutic target for regulation of progression of oral cancer.
Nozaki
Shinichi
S
Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan. snozaki@med.kanazawa-u.ac.jp
Endo
Yoshio
Y
Nakahara
Hirokazu
H
Yoshizawa
Kunio
K
Hashiba
Yukari
Y
Kawashiri
Shuichi
S
Tanaka
Akira
A
Nakagawa
Kiyomasa
K
Matsuoka
Yudai
Y
Kogo
Mikihiko
M
Yamamoto
Etsuhide
E
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000556:secondary; D002642:Chick Embryo; D006801:Humans; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000378:metabolism
D014408:Biomarkers, Tumor; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator