Fundamental study of the tumor-related amino acid transporter LAT1 for clinical application

• Project/Area Number: 26450409
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Veterinary medical science
• Research Institution: Tokyo University of Agriculture and Technology (2015-2016); Rakuno Gakuen University (2014)
• Principal Investigator: Uchide Tsuyoshi 東京農工大学, (連合)農学研究科(研究院), 特任教授 (20327456)
• Co-Investigator(Renkei-kenkyūsha): Kadosawa Tsuyoshi 酪農学園大学, 獣医学群, 教授 (70214418) ; Saida Kaname 独立行政法人産業技術総合研究所, バイオメディカル研究部門, 研究員 (00357055)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腫瘍 / アミノ酸 / トランスポーター / LAT1 / 阻害剤 / 血管肉腫 / エンドセリン / 獣医学 / 臨床 / アミノ酸トランスポーター / 犬 / 悪性黒色腫 / 阻害薬 / 乳腺腫瘍

Outline of Final Research Achievements

L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system L, transports branched or aromatic amino acids essential for fundamental cellular activities such as cellular growth, proliferation and maintenance. This amino acid transporter recently has received attention because of its preferential and up-regulated expression in a variety of human tumors in contrast to its limited distribution and low-level expression in normal tissues. In this study, we explored the feasibility of using LAT1 inhibitor as a new therapeutic agent for canine hemangiosarcoma (HSA), mammary gland tumor (MGT) and malignat melanoma (MM). The LAT1 mRNA levels in HSA, MGT and MM tissues as well as the levels in their cell lines were significantly (P<0.01) higher than in normal tissues. Functional analysis of LAT1 showed that the cellular growth activities in these cell lines were inhibited in a dose-dependent manner by selective LAT1 inhibitors.

Research Products

• [Journal Article] Characterization of feline cytochrome P450 2B6. (2017)
  • Author(s): Okamatsu G, Komatsu T, Ono Y, Inoue H, Uchide T, Onaga T, Endoh D, Kitazawa T, Hiraga T, Uno Y, Teraoka H.
  • Journal Title: Xenobiotica. Volume: 47 Issue: 2 Pages: 93-102
  • DOI: 10.3109/00498254.2016.1145754
  • Peer Reviewed
• [Journal Article] GM1 gangliosidosis in a Japanese domestic cat: a new variant identified in Hokkaido, Japan (2016)
  • Author(s): Hanazono, K., Fukumoto, S., Kawamura, Y., Endo, Y., Kadosawa, T. Iwano, H. and Uchide, T.
  • Journal Title: Journal of Veterinary Medical Science Volume: 78 Issue: 1 Pages: 91-95
  • DOI: 10.1292/jvms.15-0281
  • NAID: 130005121594
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed
• [Journal Article] Big endothelin-1 as a tumour marker for canine hemangiosarcoma. (2015)
  • Author(s): Fukumoto, S., Miyasho, T., Hanazono, K., Saida, K., Kadosawa, T., Iwano, H. and Uchide, T.
  • Journal Title: Vet. J. Volume: 204 Issue: 3 Pages: 269-274
  • DOI: 10.1016/j.tvjl.2015.03.024
  • Peer Reviewed
• [Journal Article] Ultrasonographic findings related to prognosis in canine transitional cell carcinoma. (2014)
  • Author(s): Hanazono, K., Fukumoto, S., Endo, Y., Ueno, H., Kadosawa, T. and Uchide, T.＊
  • Journal Title: Vet. Radiol. Ultrasound Volume: 55 Issue: 1 Pages: 79-84
  • DOI: 10.1111/vru.12085
  • Peer Reviewed
• [Journal Article] Extranodal lymphoma with peripheral nervous system involvement in a dog (2014)
  • Author(s): 59.Ueno, H., Miyoshi, K., Fukui, S., Kondo, U., Matsuda, K. and Uchide T
  • Journal Title: J. Vet. Med. Sci. Volume: 76 Pages: 723-727
  • NAID: 130004780995
  • Peer Reviewed
• [Presentation] L-type amino acid transporter 1(LAT1)阻害薬の犬悪性黒色腫に対する治療効果 (2015)
  • Author(s): 福本真也 河村芳朗 岩野英知 遠藤能史 廉澤剛 打出毅
  • Organizer: 第158回日本獣医学会学術集会
  • Place of Presentation: 十和田（北里大）
  • Year and Date: 2015-09-08
• [Presentation] Clinical use of serum big endothelin-1 levels as a tumour marker for haemangiosarcoma (2015)
  • Author(s): Fukumoto, S., Saida, K., Miyasho, T., Kadosawa, T., Iwano, H. and Uchide, T
  • Organizer: Fourteenth International Conference on Endothelin
  • Place of Presentation: Savannah, Georgia, USA
  • Year and Date: 2015-09-02
  • Int'l Joint Research
• [Presentation] L-type amino acid transpoter1(LAT1)阻害薬の犬悪性黒色腫に対する治療効果 (2014)
  • Author(s): 福本真也 岩野英知 遠藤能史 廉澤剛 打出毅
  • Organizer: 第157回日本獣医学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2014-09-10