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l‐type amino acid transporter 1 and CD98 expression in primary and metastatic sites of human neoplasms
Authors:Kyoichi Kaira  Noboru Oriuchi  Hisao Imai  Kimihiro Shimizu  Noriko Yanagitani  Noriaki Sunaga  Takeshi Hisada  Shigebumi Tanaka  Tamotsu Ishizuka  Yoshikatsu Kanai  Hitoshi Endou  Takashi Nakajima  Masatomo Mori
Affiliation:1. Departments of Medicine and Molecular Science;2. Diagnostic Radiology and Nuclear Medicine;3. Thoracic and Visceral Organ Surgery;4. General Surgical Science, and;5. Division of Bio‐system Pharmacology, Department of Pharmacology, Osaka University Graduate School of Medicine, 2‐2 Yamadaoka, Suita, Osaka 565‐0871;6. Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Shinkawa, Mitaka, Tokyo 181‐8611, Japan;7. Tumor Pathology, Gunma University Graduate School of Medicine, Showa‐machi, Maebashi, Gunma 371‐8511
Abstract:The significance of l ‐type amino acid transporter (LAT) 1 expression remains unclear in the metastatic process of human neoplasms, whereas experimental studies have demonstrated that LAT1 is associated with the metastatic process of cancer cells. We compared the immunohistochemical expression of LAT1 and CD98 between the primary site and a concordant pulmonary metastatic site in 93 cancer patients, all of whom had undergone thoracotomy. LAT1, CD98, Ki‐67 labeling index, vascular endothelial growth factor (VEGF), CD31, and CD34 were analyzed by immunohistochemical staining in the resected tumors of 93 cancer patients: 45 colon cancers; nine breast cancers; eight head and neck cancers; 11 genital cancers; 14 soft‐tissue sarcomas; and six other cancers. The expression of these markers was significantly higher in the metastatic sites than in the primary sites. In total, the positive rates of LAT1, CD98, Ki‐67, VEGF, CD31, and CD34 were 40, 24, 56, 41, 45, and 39%, respectively, in the primary sites and 65, 45, 84, 67, 73, and 61%, respectively, in the metastatic sites. LAT1 expression was closely correlated with CD98 expression, angiogenesis, and cell proliferation. The association between LAT1 and CD98 expression was strongest in the primary and metastatic sites. The present study suggests that overexpression of LAT1 and CD98 has an important role to play in the metastatic process of variable human neoplasms. Moreover, LAT1 expression was significantly correlated with cell proliferation and angiogenesis. (Cancer Sci 2008; 99: 2380–2386)
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