Functional analysis of Periostin in malignant melanoma

• Project/Area Number: 22791100
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: 独立行政法人医薬基盤研究所
• Principal Investigator: SERADA Satoshi 独立行政法人医薬基盤研究所, 創薬基盤研究部, 研究員 (50463302)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 癌 / periostin / Periostin

Research Abstract

Malignant melanoma is one of the most aggressive cancers, since this tumor metastasize to various organs and resistant to chemotherapy. By using quantitative proteomic apProach, we have been identified that Peroostin, one of the extracellular matrix proteins, was highly expressed in the melanoma tissue compared with normal skin tissue. This study was aimed to reveal the association between Periostin and malignant melanoma.
Recombinant Periostin protein treatment significantly accelerated the proliferation of nlelanoma cell lines (Mewo, G361 and VMRC-MELG). This growth promoting effect induced by Periostin treatment was dependent on the integrin/P44/42 MAPK signaling Pathway in vitro. To reveal the role of Periostin to the growth of the malignant nlelanoma, Periostin/RAG2 double knockout mice were developed by mating Periostin deficient mice and RAG2 deficient mice. In Periostin knockout mice and Periostin/RAG2 double knockout mice, Mewo cells were subcutaneously implanted and tumor proliferation was analyzed. Compared with Periostin knockout mice, the tumor proliferation of Mewo was significantly delayed in Periostin/RAG2 double knockout mice, demonstrating that Periostin also induce proliferation of melanoma cells in vivo. These results suggest that Periostin induces proliferation of tumor cells in vi tzO and in vivo and Periostin would be a promising therapeutic target of malignant melanoma.

Research Products

• [Journal Article] Periostin Facilitates Skin Sclerosis via PI3K/Akt Dependent Mechanism in a Mouse Model of Scleroderma (2012)
  • Author(s): Yang L, Serada S, Fujimoto M, Terao M, Kotobuki Y, Kitaba S, Matsui S, Kudo A, Naka T, Murota H, Katayama I
  • Journal Title: PLoS One Volume: 7(7)
• [Journal Article] Periostin, a matricellular protein (2012)
  • Author(s): Ontsuka K, Kotobuki Y, Shiraishi H, Serada S, Ohta S, Tanemura A, Yang L, Fujimoto M, Arima K, Suzuki S, Murota H, Toda S, Kudo A, Conway S, Narisawa Y, Katayama I, Izuhara K, Naka T
  • Journal Title: accelerates cutaneous wound repair by activating dermal fibroblasts Experimental Dermatology Volume: 21(5) Pages: 331-336
• [Journal Article] Dysregulation of Melanocyte Function by Th17-related Cytokines: Significance of Th17 Cell Infiltration in Autoimmune Vitiligo Vulgaris (2012)
  • Author(s): Kotobuki Y, Tanemura A, Yang L, Itoi S, Kaneda M, Murota H, Fujimoto M, Serada S, Naka T Katayama I
  • Journal Title: Pigment Cell Melanoma Res Volume: 25(2) Pages: 219-30
• [Journal Article] Anti-proliferative effect of SOCS-1 through the suppression of STAT3 and p38 MAPK activation in gastric cancer cells (2012)
  • Author(s): Souma Y, Nishida T, Serada S, Iwahori K, Takahashi T, Fujimoto M, Ripley B, Nakajima K, Miyazaki Y, Mori M, Doki Y, Sawa Y, Naka T
  • Journal Title: Int J Cancer Volume: 131(6) Pages: 1287-96
• [Journal Article] Serum leucine-rich alpha-2 glycoprotein is a disease activity biomarker in ulceratiVe colitis (2012)
  • Author(s): Serada S, Fujimoto M, Terabe F, Iijima H, Shinzaki S, Matsuzaki S, Ohkawara T, Nezu R, Nakajima S, Kobayashi T, Plevy SE, Takehara T, Naka T
  • Journal Title: Inflamm Bowel Dis Volume: 18(11) Pages: 2169-79
• [Journal Article] Periostin Facilitates Skin Sclerosis via PI3K/Akt Dependent Mechanism in a Mouse Model of Scleroderma (2012)
  • Author(s): Yang L, Serada S, Fujimoto M, Terao M, Kotobuki Y, Kitaba S, Matsui S, Kudo A, Naka T, Murota H, Katayama I
  • Journal Title: PLoS One Volume: 7(7) Issue: 7 Pages: e41994-e41994
  • DOI: 10.1371/journal.pone.0041994
  • Peer Reviewed
• [Journal Article] Periostin, a matricellular protein, accelerates cutaneous wound repair by activating dermal fibroblasts (2012)
  • Author(s): Ontsuka K, Kotobuki Y, Shiraishi H, Serada S, Ohta S, Tanemura A, Yang L, Fujimoto M, Arima K, Suzuki S, Murota H, Toda S, Kudo A, Conway S, Izuhara K, Katayama I, Naka T
  • Journal Title: Experimental Dermatology Volume: 21(5) Issue: 5 Pages: 331-336
  • DOI: 10.1111/j.1600-0625.2012.01454.x
  • Peer Reviewed
• [Journal Article] Serum leucine-rich alpha-2 glycoprotein is a disease activity biomarker in ulcerative colitis (2012)
  • Author(s): Serada S, Fujimoto M, Terabe F, Iijima H, Shinzaki S, Matsuzaki S, Ohkawara T, Nezu R, Nakajima S, Kobayashi T, Plevy SE, Takehara T, Naka T
  • Journal Title: Inflamm Bowel Dis Volume: (In Press)
  • Peer Reviewed
• [Journal Article] Blockade of Interleukin-6 Signaling Suppresses Not Only Th17 But Also Interphotoreceptor Retinoid Binding Protein-Specific Thl By Promoting Regulatory T cell In Experimental Autoimmune Uveoretinitis (2011)
  • Author(s): Haruta H, Ohguro N, Fujimoto M, Hohki S, Terabe F, Serada S, Nomura S, Nishida K, Kishimoto T, Naka T
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 52 Pages: 3264-71
• [Journal Article] The Influence of Excessive IL-6 Production In Vivo on the Development and Function of Foxp3+ Regulatory T Cells (2011)
  • Author(s): Fujimoto M, Nakano M, Terabe F, Kawahata H, Ohkawara T, Han Y, Ripley B, Serada S, Nishikawa T, Kimura A, Nomura S, Kishimoto T, Naka T
  • Journal Title: J Immunol Volume: 186(1) Pages: 32-40
• [Journal Article] Overexpression of SOCS3 exhibits preclinical antitunlor activity against malignant pleural mesothelioma (2011)
  • Author(s): Iwahori K, Serada S, Fujimoto M, Nomura S, Osaki T, Chun Man Lee, Mizuguchi H, Takahashi T, Ripley B, Okumura M, Kawase I, Kishimoto T, Naka T
  • Journal Title: Int J Cancer Volume: 129(4) Pages: 1005-17
• [Journal Article] Comparative analysis of the effects of anti-IL-6 receptor mAb and anti-TNF mAb treatment on CD4+ T-cell responses in murine colitis (2011)
  • Author(s): Terabe F, Fujimoto M, Serada S, Shinzaki S, Iijima H, Tsujii M, Hayashi N, Nomura S, Kawahata H, Myoung Ho Jang, Miyasaka M, Mihara M, Ohsugi Y, Kishimoto T, Naka T
  • Journal Title: Inflamm Bowel Dis Volume: 17(2) Pages: 491-502
• [Journal Article] Dysregulation of Melanocyte Function by Th17-related Cytokines : Significance of Th17 Cell Infiltration in Autoimmune Vitiligo Vulgaris (2011)
  • Author(s): Kotobuki Y, Tanemura A, Yang L, Itoi S, Kaneda M, Murota H, Fujimoto M, Serada S, Naka T, Katayama I
  • Journal Title: Pigment Cell & Melanoma Research Volume: (In Press)
  • Peer Reviewed
• [Journal Article] Anti-proliferative effect of SOCS-1 through the suppression of STAT3 and p38 MAPK activation in gastric cancer cells (2011)
  • Author(s): Souma Y, Nishida T, Serada S, Iwahori K, Takahashi T, Fujimoto M, Ripley B, Nakajima K, Miyazaki Y, Mori M, Doki Y, Sawa Y, Naka T
  • Journal Title: Int J Cancer Volume: (In Press)
  • Peer Reviewed
• [Journal Article] Blockade of Interleukin-6 Signaling Suppresses Not Only Th17 But Also Interphotoreceptor Retinoid Binding Protein-Specific Th1 By Promoting Regulatory T cells In Experimental Autoimmune Uveoretinitis (2011)
  • Author(s): Haruta H, Ohguro N, Fujimoto M, Hohki S, Terabe F, Serada S, Nomura S, Nishida K, Kishimoto T, Naka T
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 52 Pages: 3264-71
  • Peer Reviewed
• [Journal Article] The Influence of Excessive IL-6 Production In Vivo on the Development and Function of Foxp3+ Regulatory T Cells. (2011)
  • Author(s): Fujimoto M, Nakano M, Terabe F, Kawahata H, Ohkawara T, Han Y, Ripley B, Serada S, Nishikawa T, Kimura A, Nomura S, Kishimoto T, Naka T.
  • Journal Title: Journal of Immunology Volume: (In press)
  • Peer Reviewed
• [Journal Article] Overexpression of SOCS3 exhibits preclinical antitumor activity against malignant pleural mesothelioma (2011)
  • Author(s): Iwahori K, Serada S, Fujimoto M, Nomura S, Osaki T, Chun Man Lee, Mizuguchi H, Takahashi T, Ripley B, Okumura M, Kawase I, Kishimoto T, Naka T
  • Journal Title: International Journal of Cancer Volume: (In press)
  • Peer Reviewed
• [Journal Article] Comparative analysis of the effects of anti-IL-6 receptor mAb and anti-TNF mAb treatment on CD4+ T-cell responses in murine colitis (2011)
  • Author(s): Terabe F, Fujimoto M, Serada S, Shinzaki S, Iijima H, Tsujii M, Hayashi N, Nomura S, Kawahata H, Myoung Ho Jang, Miyasaka M, Mihara M, Ohsugi Y, Kishimoto T, Naka T
  • Journal Title: Inflammatory Bowel Diseases Volume: 17 Pages: 491-502
  • Peer Reviewed
• [Journal Article] Blockade of Interleukin-6 Signaling SupPresses Experimental Autoimmune Uveoretinitis by the Inhibition of Inflammatory Th17 Responses (2010)
  • Author(s): Hohki S, Ohguro N, Haruta H, Nakai K, Terabe F, Serada S, Fujimoto M, Nomura S, Kawahata H, Kishimoto T, Naka T
  • Journal Title: Exp Eye Res Volume: 91(2) Pages: 162-70
• [Journal Article] iTRAQ-based proteomic identification of leucine rich alpha 2 glycoprotein (LRG) as a novel inflammatory biomarker in autoimmune diseases (2010)
  • Author(s): Serada S, Fujimoto M, Ogata A, Terabe F, Hirano T, Iijima H, Shinzaki S, Nishikawa T, Ohkawara T, Iwahori K, Ohguro N, Kishimoto T, Naka T
  • Journal Title: Ann Rheum Dis Volume: 69 Pages: 770-774
• [Journal Article] Blockade of Interleukin-6 Signaling Suppresses Experimental Autoimmune Uveoretinitis by the Inhibition of Inflammatory Th17 Responses. (2010)
  • Author(s): Hohki S, Ohguro N, Haruta H, Nakai K, Terabe F, Serada S, Fujimoto M, Nomura S, Kawahata H, Kishimoto T, Naka T.
  • Journal Title: Experimental Eye Research. Volume: 91 Pages: 162-170
  • Peer Reviewed
• [Journal Article] iTRAQ-based proteomic identification of leucine rich alpha 2 glycoprotein (LRG) as a novel inflammatory biomarker in autoimmune diseases (2010)
  • Author(s): Serada S, Fujimoto M, Ogata A, Terabe F, Hirano T, Iijima H, Shinzaki S, Nishikawa T, Ohkawara T, Iwahori K, Ohguro N, Kishimoto T, Naka T
  • Journal Title: Annals of the Rheumatic Diseases Volume: 69 Pages: 770-774
  • Peer Reviewed
• [Presentation] Quantitative proteomic analysis of tumor growth associated proteins in cutaneous malignant melanoma Short title: Proteomics of melanoma (2012)
  • Author(s): Satoshi Serada, Yorihisa Kotobuki, Atsushi Tanemura, Ichiro Katayama, Tetsuji Naka
  • Organizer: 103rd Annual Meeting of the American Association for Cancer Research;2012
  • Place of Presentation: 米国(シカゴ)
  • Year and Date: 2012-04-02
• [Presentation] Heterogeneous Nuclear RNP-K Is a Novel Cold-Related Autoantigen in Patients with Raynaud' s Phenomenon (2012)
  • Author(s): Satoshi Serada, Minoru Fujimoto, Tetsuji Naka
  • Organizer: ACR/ARHP Annual Meeting, in Washington, DC, November 09-14, 2012. November 12 (ACR 2012第78回米国リウマチ学会議)
  • Place of Presentation: 米国(ワシントン)
• [Presentation] 定量的リン酸化プロテオーム解析による消化管間質腫瘍のイマチニブ耐性因子の探索 (2012)
  • Author(s): 世良田聡,高橋剛,浦瀬真伊子,藤本穣,原田絵美,西田俊朗,仲哲治
  • Organizer: 第10回日本ヒトプロテオーム学会
  • Place of Presentation: 本科学未来館7階(東京)
• [Presentation] Periostin, a matricellular protein, accelerates wound repair by activating dermal fibroblasts (2011)
  • Author(s): Yorihisa Kotobuki, Kanako Ontsuka, Satoshi Serada, Hiroshi Shiraishi, Atsushi Tanemura, Shoichiro Ohta, Lingli Yang, Tetsuji Naka, Kenji Izuhara, Ichiro Katayama
  • Organizer: 第36回日本研究皮膚科学会学術大会・総会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2011-12-09
• [Presentation] 定量的プロテオーム解析による子宮内膜癌抗原蛋白質の探索 (2011)
  • Author(s): Satoshi Serada, Takuhei Yokoyama, Takayuki Enomoto, Shinya Matsuzaki, Akiko Morimoto, Ayako Kim, Minoru Fujimoto, Tadashi Kimura, Tetsuji Naka
  • Organizer: 第9回日本プロテオーム学会
  • Place of Presentation: 新潟市朱鷺メッセ
  • Year and Date: 2011-07-29
• [Presentation] Leucine rich alpha 2 glycoprotein (LRG) is a novel biomarker for monitoring disease activity in patients with Ulcerative Colitis (2011)
  • Author(s): Satoshi Serada, Minoru Fujimoto, Fumitaka Terabe, Tetsuji Naka
  • Organizer: 第40回日本免疫学会総会
  • Place of Presentation: 幕張メッセ(千葉市)
• [Presentation] Periostin, a matricellular protein, accelerates wound repair by activating dermal fibroblasts (2011)
  • Author(s): Yorihisa Kotobuki, Kanako Ontsuka, Satoshi Serada, Hiroshi Shiraishi, Atsushi Tanemura, Shoichiro Ohta, Lingli Yang, Tetsuji Naka, Kenji Izuhara, Ichiro Katayama
  • Organizer: 第36回日本研究皮膚科学会学術大会・総会
  • Place of Presentation: 国立京都国際会館(京都市)
• [Presentation] 定量的プロテオーム解析による子宮内膜癌抗原蛋白質の探索 (2011)
  • Author(s): 世良田聡,横山拓平,榎本隆之,松崎慎哉,森本晶子,金雅子,藤本穣,木村正,仲哲治
  • Organizer: 第9回 日本プロテオーム学会
  • Place of Presentation: 新潟市朱鷺メッセ2階(新潟市)
• [Presentation] lLabotatory For Immune Signal, National Institute of Biomedical Innovation, Ibaraki City (Osaka)/JAPAN, 2 Surgery, Osaka University, Suita/JAPAN, 3 Surgery, Osaka Police Hospital, Osaka/JAPAN, 4 Laboratory For Immune Signal, National Institute of Biomedical Innovation, Ibaraki City (Osaka)/JAPAN (2010)
  • Author(s): S. Serada, Y. Souma, T. Nishida, M. Fujimoto, T. Naka
  • Organizer: SOCS-1,-3 GENE DELIVERY IN GASTRIC CANCER CELLS INDUCES A POTENT ANTI-PROLIFERATIVE EFFECT VIA THE SUPPRESSION OF JAK/STAT AND P38 MAPK S IGNAL ING PATHWAYS
  • Place of Presentation: イタリア(ミラノ)
  • Year and Date: 2010-10-09
• [Presentation] SOCS-1,-3 GENE DELIVERY IN GASTRIC CANCER CELLS INDUCES A POTENT ANTI-PROLIFERATIVE EFFECT VIA THE SUPPRESSION OF JAK/STAT AND P38 MAPK SIGNALING PATHWAYS (2010)
  • Author(s): Serada S, Souma Y, Nishida T, Fujimoto M, Naka T
  • Organizer: 35th ESMO Congress
  • Place of Presentation: イタリア(ミラノ)
  • Year and Date: 2010-10-09
• [Presentation] 自己免疫疾患の新規活動性マーカーとしてのleucine rich alpha 2 glycoprotein Proteomics-based identification of leucine rich alpha 2 glycoprotein(LRG)as a novel biomarker associated with disease activity of inflammatory autoimmune disorders (2010)
  • Author(s): 世良田聡、藤本穣、寺部文隆、西川哲平、仲哲治
  • Organizer: 第8回 日本プロテオーム学会
  • Place of Presentation: 千葉
  • Year and Date: 2010-07-26
• [Presentation] 自己免疫疾患の新規活動性マーカーとしてのleucine rich alpha 2 glycoprotein (2010)
  • Author(s): 世良田聡、藤本穣、寺部文隆、西川哲平、仲哲治
  • Organizer: 第8回 日本プロテオーム学会
  • Place of Presentation: 東京ベイホテル東急(浦安市)
• [Presentation] Quantitative proteomic analysis of tumor growth associated proteins in cutaneous malignant melanoma
  • Author(s): Serada S, Kotobuki Y, Tanemura A, Katayama I, Naka T
  • Organizer: 103rd Annual Meeting of the American Association for Cancer Research
  • Place of Presentation: 米国（シカゴ）
• [Book] サイトカインシグナル伝達抑制分子(SOCS)の新規抗癌剤としての応用 (2010)
  • Author(s): 世良田聡,仲哲治
  • Publisher: 医歯薬出版株式会社, 医学のあゆみ,234(5)
• [Book] 医学のあゆみサイトカインシグナル伝達抑制分子(SOCS)の新規抗癌剤としての応用 (2010)
  • Author(s): 世良田聡, 仲哲治
  • Publisher: 医歯薬出版株式会社
• [Patent(Industrial Property Rights)] 創傷治癒剤 (2010)
  • Inventor(s): 寿 順久、世良田 聡、仲 哲治
  • Industrial Property Rights Holder: 財団法人ヒューマンサイエンス振興財団
  • Industrial Property Number: 2010-151139
  • Filing Date: 2010-07-01
• [Patent(Industrial Property Rights)] 創傷治癒剤 (2010)
  • Inventor(s): 寿順久、世良田聡、仲哲治
  • Industrial Property Rights Holder: 財団法人ヒューマンサイエンス振興財団
  • Industrial Property Number: 2010-151139
  • Filing Date: 2010-07-01