title: Tie2 Regulates Tumor Metastasis of Oral Squamous Cell Carcinomas.
abstract: The endothelial-specific receptor, tyrosine kinase with immunoglobulin-like loops and epidermal growth factor homology domains-2 (Tie2) is a member of the tyrosine kinase family and is ubiquitous in normal tissues; however, little is known about the mechanisms and roles of Tie2 in oral squamous cell carcinomas (OSCCs). In the current study, we investigated the expression status of Tie2 in OSCCs by quantitative reverse transcriptase-polymerase chain reaction, immunoblotting, and immunohistochemistry and the functional mechanisms of Tie2 using its overexpressed OSCC (oeTie2) cells and Tie2 blocking by its antibody. We found that Tie2 expression was down-regulated significantly (p < 0.05) in OSCCs compared with normal counterparts in vitro and in vivo. Interestingly, oeTie2 cells showed higher cellular adhesion (p < 0.05) and lower cellular invasion (p < 0.05) compared with control cells; whereas there was similar cellular proliferation in both transfectants. Furthermore, cellular adhesion was inhibited and invasion was activated by Tie2 function-blocking antibody (p < 0.05), indicating that Tie2 directly regulates cellular adhesion and invasion. As expected, among the clinical variables analyzed, Tie2-positivity in patients with OSCC was correlated closely with negative lymph node metastasis. These results suggested for the first time that Tie2 plays an important role in tumor metastasis and may be a potential biomarker for OSCC metastasis.
authors.affiliation: 1. Department of Oral Science Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kitajima
authors.affiliation: 2. Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kasamatsu
authors.affiliation: 1. Department of Oral Science Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;
authors.forename: Dai
authors.initials: D
authors.lastname: Nakashima
authors.affiliation: 1. Department of Oral Science Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;
authors.forename: Isao
authors.initials: I
authors.lastname: Miyamoto
authors.affiliation: 1. Department of Oral Science Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: 1. Department of Oral Science Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Saito
authors.affiliation: 3. Department of Environmental Health Science and.
authors.forename: Takane
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: 2. Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Endo-Sakamoto
authors.affiliation: 4. Department of Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiiba
authors.affiliation: 1. Department of Oral Science Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;; 2. Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanzawa
authors.affiliation: 1. Department of Oral Science Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;; 2. Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Uzawa
keywords: Oral Cancer; Tie2