Nozaki Shinichi, Endo Yoshio, Nakahara Hirokazu, Yoshizawa Kunio, Hashiba Yukari, Kawashiri Shuichi, Tanaka Akira, Nakagawa Kiyomasa, Matsuoka Yudai, Kogo Mikihiko, Yamamoto Etsuhide
Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan.
Oral Oncol. 2005 Nov;41(10):971-7. doi: 10.1016/j.oraloncology.2005.05.013. Epub 2005 Aug 29.
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.
有报道称，多种癌症的不良预后与尿激酶型纤溶酶原激活剂（uPA）及其表面受体（uPAR）的伴随表达之间存在强相关性。我们和其他人之前已经表明，uPA系统在一部分头颈部鳞状细胞癌中起重要作用。在本研究中，我们发现uPAR是高恶性口腔癌细胞（OSC-19）侵袭和转移所必需的。用靶向uPAR的反义寡核苷酸（AS）处理OSC-19细胞导致uPAR mRNA表达显著降低。此外，用靶向uPAR的AS或siRNA预处理可抑制实验模型中OSC-19细胞的进展。这些结果表明，uPAR的过表达增加了OSC-19细胞的侵袭性和转移性，并且uPAR是调节口腔癌进展的一个有前景的治疗靶点。
