Proteomic screening for malignant melanoma antigen and development of antibody-based medicine for metastasis.

• Project/Area Number: 25670508
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: National Institutes of Biomedical Innovation, Health and Nutrition
• Principal Investigator: NAKA TETSUJI 国立研究開発法人医薬基盤・健康・栄養研究所, 免疫シグナルプロジェクト, シニアプロジェクトリーダー (30303936)
• Co-Investigator(Renkei-kenkyūsha): FUJIMOTO MINORU 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 免疫シグナルプロジェクト, 主任研究員 (00379190) ; SERADA SATOSHI 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 免疫シグナルプロジェクト, 研究員 (50463302)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 癌 / プロテオーム / タンパク質 / 抗体 / 悪性黒色腫 / 抗体医薬 / 蛋白質

Outline of Final Research Achievements

By quantitative proteomic approach, cell surface membrane proteins were screened by comparing normal human melanocytes and malignant melanoma cell lines. Elevated expression levels of the melanoma candidate antigen,Lipolysis-stimulated lipoprotein receptor (LSR), was confirmed by FACS analysis against cell lines compared to normal melanocytes. By immunohistochemical staining analysis, increased expression levels of the melanoma candidate antigen was also confirmed using malignant melanoma tissue sections. We developed 6 clones of novel chicken/mouse chimeric monoclonal antibody targeting this antigen. Several clones showed direct tumor growth inhibition in vitro. The detailed mechanisms of anti-tumor effects were investigated in vitro and in vivo.

Research Products

• [Journal Article] CpG ODN potentiates the anti-tumor activity of anti-BST2 antibody. (2015)
  • Author(s): Hiramatsu, K., Serada, S., Kobiyama, K., Nakagawa, S., Morimoto, A., Matsuzaki, S., Ueda,Y., Fujimoto, M., Yoshino, K., Ishii, K., Enomoto, T., Kimura, T., Naka, T.
  • Journal Title: Cancer Science Volume: 106(10) Issue: 10 Pages: 474-82
  • DOI: 10.1111/cas.12738
  • Peer Reviewed / Open Access
• [Journal Article] Suppressor of cytokine signalling-1 induces significant preclinical antitumor effect in malignant melanoma cells. (2015)
  • Author(s): Tagami-Nagata N, Serada S, Fujimoto M, Tanemura A, Nakatsuka R, Ohkawara T, Murota H, Kishimoto T, Katayama I, Naka T.
  • Journal Title: Exp Dermatol. Volume: 24 Issue: 11 Pages: 864-71
  • DOI: 10.1111/exd.12802
  • Peer Reviewed
• [Journal Article] Gene therapy with SOCS1 for gastric cancer induces G2/M arrest and has an anti-tumor effect on peritoneal carcinomatosis. (2015)
  • Author(s): Natatsuka R, Takahashi T, Serada S, Fujimoto M, Ookawara T, Nishida T, Hara H, Nishigaki T, Harada E, Murakami T, Miyazaki Y, Makino T, Kurokawa Y, Yamasaki M, Miyata H, Nakajima K, Takiguchi S, Kishimoto T, Mori M, Doki Y, Naka T.
  • Journal Title: Br J Cancer Volume: 113(3) Issue: 3 Pages: 433-442
  • DOI: 10.1038/bjc.2015.229
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Proteomic identification of heterogeneous nuclear ribonucleoprotein K as a novel cold-associated autoantigen in patients with secondary Raynaud's phenomenon. (2015)
  • Author(s): Yang L, Fujimoto M, Murota H, Serada S, Fujimoto M, Honda H, Yamada K, Suzuki K, Nishikawa A, Hosono Y, Yoneda Y, Takehara K, Imura Y, Mimori T, Takeuchi T, Katayama I, Naka T.
  • Journal Title: Rheumatology (Oxford). Volume: 54 Issue: 2 Pages: 349-58
  • DOI: 10.1093/rheumatology/keu325
  • Peer Reviewed
• [Journal Article] Leucine-rich α-2-glycoprotein promotes TGFβ1-mediated growth suppression in the Lewis lung carcinoma cell lines. (2015)
  • Author(s): Takemoto N, Serada S, Fujimoto M, Honda H, Ohkawara T, Takahashi T, Nomura S, Inohara H, Naka T.
  • Journal Title: Oncotarget Volume: In Press
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Periostin accelerates human malignant melanoma progression by modificating the melanoma microenvironment (2014)
  • Author(s): Kotobuki Y, Tanemura A, Serada S, Yang L, Nomura S, Kudo A, Izuhara K, Murota H, Fujimoto M, Katayama I, Naka T
  • Journal Title: Pigment Cell Melanoma Res Volume: 27 Issue: 4 Pages: 630-639
  • DOI: 10.1111/pcmr.12245
  • Peer Reviewed / Open Access
• [Journal Article] Annexin A4 induces platinum resistance in a chloride-and calcium-dependent manner. (2014)
  • Author(s): Morimoto A, Serada S, Enomoto T, Kim A, Matsuzaki S, Takahashi T, Ueda Y, Yoshino K, Fujita M, Fujimoto M, Kimura T, Naka T.
  • Journal Title: Oncotarget Volume: 5 Pages: 7776-87
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Calretinin mediates apoptosis in small cell lung cancer cells expressing tetraspanin CD9. (2013)
  • Author(s): He P, Kuhara H, Tachibana I, Jin Y, Takeda Y, Tetsumoto S, Minami T, Kohmo S, Hirata H, Takahashi R, Inoue K, Nagatomo I, Kida H, Kijima T, Naka T, Morii E, Kawase I, Kumanogoh A.
  • Journal Title: FEBS Open Bio. Volume: 3 Issue: 1 Pages: 225-30
  • DOI: 10.1016/j.fob.2013.04.005
  • Peer Reviewed
• [Journal Article] D34(+) /CD38(-) acute myelogenous leukemia cells aberrantly express CD82 which regulates adhesion and survival of leukemia stem cells. (2013)
  • Author(s): Nishioka C, Ikezoe T, Furihata M, Yang J, Serada S, Naka T, Nobumoto A, Kataoka S, Tsuda M, Udaka K, Yokoyama A
  • Journal Title: International Journal of Cancer Volume: 132(9) Issue: 9 Pages: 2006-2019
  • DOI: 10.1002/ijc.27904
  • Peer Reviewed
• [Journal Article] Molecular mechanism underlying the antiproliferative effect of suppressor of cytokine signaling-1 in non-small-cell lung cancer cells. (2013)
  • Author(s): Shimada K, Serada S, Fujimoto M, Nomura S, Nakatsuka R, Harada E, Iwahori K, Tachibana I, Takahashi T, Kumanogoh A, Kishimoto T, Naka T.
  • Journal Title: Cancer Sci. Volume: 104 Issue: 11 Pages: 1483-91
  • DOI: 10.1111/cas.12266
  • Peer Reviewed
• [Journal Article] New findings of kinase switching in gastrointestinal stromal tumor under imatinib using phosphoproteomic analysis. (2013)
  • Author(s): Takahashi T, Serada S, Ako M, Fujimoto M, Miyazaki Y, Nakatsuka R, Ikezoe T, Yokoyama A, Taguchi T, Shimada K, Kurokawa Y, Yamasaki M, Miyata H, Nakajima K, Takiguchi S, Mori M, Doki Y, Naka T, Nishida T.
  • Journal Title: Int J Cancer Volume: 133(11) Pages: 2737-2743
  • DOI: 10.1002/ijc.28282
  • Peer Reviewed