Analysis on the role of CEACAM1 in human mastocytosis

• Project/Area Number: 15K08362
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Kyoto University
• Principal Investigator: Kataoka Tatsuki 京都大学, 医学研究科, 講師 (20343254)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: マスト細胞 / CEACAM1 / KIT / SHP-1 / 甲状腺髄様癌 / Src family kinases / マストサイトーシス

Outline of Final Research Achievements

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed in a number of tumor cell types. The immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing isoforms of this molecule which possess a long cytoplasmic tail (CEACAM1-L) generally play inhibitory roles in cell function by interacting with Src homology 2 domain-containing tyrosine phosphatase (SHP)-1 and/or SHP-2. We found that CEACAM1 was uniquely expressed at high levels in human mastocytosis. This expression was mainly derived from CEACAM1-L isoforms based upon assessment of CEACAM1 mRNA expression. CEACAM1 knockdown upregulated cell growth of HMC1.2 cells harboring KIT mutations detected in clinical mastocytosis. Immunoblotting, ELISA and immunoprecipitaion analysis showed that activated SHP-1 is preferentially associated with CEACAM1 in HMC1.2 cells harboring KIT mutations.

Research Products

• [Journal Article] Angiolymphoid hyperplasia with eosinophilia: A case of spontaneous partial regression post-biopsy. (2018)
  • Author(s): Cho M, Kaku Y, Goto K, Endo Y, Kataoka T, Otsuka A, Kabashima K.
  • Journal Title: J Dermatol Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Mast Cells Exhibiting Strong Cytoplasmic Staining for IgE and High Affinity IgE Receptor are Increased in IgG4-Related Disease. (2018)
  • Author(s): Nishida K, Gion Y, Takeuchi M, Tanaka T, Kataoka TR, Yoshino T, Sato Y.
  • Journal Title: Sci Rep Volume: 8 Issue: 1 Pages: 4656-4656
  • DOI: 10.1038/s41598-018-23043-9
  • NAID: 120006517902
  • Peer Reviewed / Open Access
• [Journal Article] RUNX transcription factors potentially control E-selectin expression in the bone marrow vascular niche in mice. (2018)
  • Author(s): Morita K, Tokushige C, Maeda S, Kiyose H, Noura M, Iwai A, Yamada M, Kashiwazaki G, Taniguchi J, Bando T, Hirata M, Kataoka TR, Nakahata T, Adachi S, Sugiyama H, Kamikubo Y.
  • Journal Title: Blood Adv Volume: 2 Issue: 5 Pages: 509-515
  • DOI: 10.1182/bloodadvances.2017009324
  • Peer Reviewed / Open Access
• [Journal Article] SLAM family member 8 is involved in oncogenic KIT-mediated signaling in human mastocytosis. (2018)
  • Author(s): Sugimoto A, Kataoka TR, Ueshima C, Takei Y, Kitamura K, Hirata M, Nomura T, Haga H.
  • Journal Title: Exp Dermatol Volume: - Issue: 6 Pages: 641-646
  • DOI: 10.1111/exd.13523
  • Peer Reviewed / Open Access
• [Journal Article] Total cell necrosis of metastatic malignant melanoma at the regional lymph node in a patient treatment with nivolumab. (2018)
  • Author(s): Komori T, Otsuka A, Kaku Y, Irie H, Honda T, Hirata M, Kataoka TR, Kabashima K.
  • Journal Title: J Dermatol Volume: 45 Issue: 1
  • DOI: 10.1111/1346-8138.14040
  • Peer Reviewed
• [Journal Article] Angiomatoid fibrous histiocytoma of the scalp mimicking cutaneous angiosarcoma in incisional biopsy containing CD31-positive histiocytes: A potential histopathological pitfall. (2018)
  • Author(s): Kanameishi S, Kaku Y, Goto K, Ishida Y, Endo Y, Dainichi T, Sakurai T, Kataoka T, Miyagawa-Hayashino A, Kabashima K.
  • Journal Title: J Dermatol Volume: 45 Issue: 2 Pages: 235-237
  • DOI: 10.1111/1346-8138.13843
  • Peer Reviewed
• [Journal Article] Genetic regulation of the RUNX transcription factor family has antitumor effects. (2017)
  • Author(s): Morita K, Suzuki K, Maeda S, Matsuo A, Mitsuda Y, Tokushige C, Kashiwazaki G, Taniguchi J, Maeda R, Noura M, Hirata M, Kataoka T, Yano A, Yamada Y, Kiyose H, Tokumasu M, Matsuo H, Tanaka S, Okuno Y, Muto M, Naka K, Ito K, Kitamura T, Kaneda Y, Liu PP, Bando T, Adachi S, Sugiyama H, Kamikubo Y.
  • Journal Title: J Clin Invest. Volume: 127(7) Issue: 7 Pages: 2815-2828
  • DOI: 10.1172/jci91788
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Killer cell immunoglobulin-like receptor 2DL4 is expressed in and suppresses the cell growth of Langerhans cell histiocytosis. (2017)
  • Author(s): Takei Y, Ueshima C, Kataoka TR, Hirata M, Sugimoto A, Rokutan-Kurata M, Moriyoshi K, Ono K, Murakami I, Iwamoto S, Haga H.
  • Journal Title: Oncotarget Volume: 8 Issue: 23 Pages: 36964-36972
  • DOI: 10.18632/oncotarget.16936
  • Peer Reviewed / Open Access
• [Journal Article] Downregulation of neuropilin-1 on macrophages modulates antibody-mediated tumoricidal activity (2017)
  • Author(s): Kawaguchi Kosuke、Suzuki Eiji、Nishie Mariko、Kii Isao、Kataoka Tatsuki R.、Hirata Masahiro、Inoue Masashi、Pu Fengling、Iwaisako Keiko、Tsuda Moe、Yamaguchi Ayane、Haga Hironori、Hagiwara Masatoshi、Toi Masakazu
  • Journal Title: Cancer Immunology, Immunotherapy Volume: 66 Issue: 9 Pages: 1131-1142
  • DOI: 10.1007/s00262-017-2002-2
  • Peer Reviewed
• [Journal Article] Maculopapular rash during a nadir period in a patient with acute myeloid leukaemia. (2017)
  • Author(s): Komori T, Kogame T, Nomura T, Kaku Y, Endo Y, Ueshima C, Hirata M, Kataoka TR, Kawabata H, Kabashima K.
  • Journal Title: Eur J Dermatol Volume: 27 Issue: 3 Pages: 316-317
  • DOI: 10.1684/ejd.2017.2991
  • Peer Reviewed
• [Journal Article] CEACAM1 long isoform has opposite effects on the growth of human mastocytosis and medullary thyroid carcinoma cells. (2017)
  • Author(s): Chiyuki Ueshima, Tatsuki R. Kataoka, Yusuke Takei, Masahiro Hirata, Akihiko Sugimoto, Mitsuyoshi Hirokawa, Yoshimichi Okayama, Richard S. Blumberg, Hironori Haga.
  • Journal Title: Cancer med. Volume: - Issue: 4 Pages: 845-856
  • DOI: 10.1002/cam4.1050
  • NAID: 120006309310
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Infiltration of PD-1-positive cells in combination with tumor site PD-L1 expression is a positive prognostic factor in cutaneous angiosarcoma. (2017)
  • Author(s): Honda Y, Otsuka A, Ono S, Yamamoto Y, Seidel JA, Morita S, Hirata M, Kataoka TR, Takenouchi T, Fujii K, Kanekura T, Okubo Y, Takahashi K, Yanagi T, Hoshina D, Hata H, Abe R, Fujimura T, Funakoshi T, Yoshino K, Masuzawa M, Amoh Y, Tanaka R, Fujisawa Y, Honda T, Kabashima K.
  • Journal Title: Oncoimmunology. Volume: 6 Issue: 1 Pages: e1253657-e1253657
  • DOI: 10.1080/2162402x.2016.1253657
  • Peer Reviewed / Open Access
• [Journal Article] Possible inducible skin-associated lymphoid tissues (iSALT)-like structures with CXCL13+ fibroblast-like cells in secondary syphilis (2017)
  • Author(s): Kogame T, Nomura T, Kataoka T, Hirata M, Ueshima C, Matsui M, Kabashima K
  • Journal Title: Br J Dermatol Volume: in press Issue: 6 Pages: 1737-1739
  • DOI: 10.1111/bjd.15349
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Perivascular epithelioid cell tumor of the descending colon mimicking a gastrointestinal stromal tumor: a case report. (2016)
  • Author(s): Iwamoto R, Kataoka TR, Furuhata A, Ono K, Hirota S, Kawada K, Sakai Y, Haga H.
  • Journal Title: World J Surg Oncol. Volume: 14 Pages: 285-285
  • NAID: 120005973379
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Clinical, Morphologic, and Pathologic Features Associated With Increased FDG Uptake in Schwannoma. (2016)
  • Author(s): Miyake KK, Nakamoto Y, Kataoka TR, Ueshima C, Higashi T, Terashima T, Nakatani K, Saga T, Minami S, Togashi K.
  • Journal Title: AJR Am J Roentgenol. Volume: 207 Pages: 1288-1296
  • Peer Reviewed / Open Access
• [Journal Article] Loss of Hep Par 1 immunoreactivity in the livers of patients with carbamoyl phosphate synthetase 1 deficiency (2016)
  • Author(s): Yamaguchi M, Kataoka TR, Shibayama T, Fukuda A, Nakazawa A, Minamiguchi S, Sakurai T,Miyagawa-Hayashino A, Yorifuji T, Kasahara M, Uemoto S, Haga H
  • Journal Title: Pathol Int Volume: 66 Issue: 6 Pages: 333-336
  • DOI: 10.1111/pin.12414
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Successful treatment with anti-TNF-alpha antibody for localised lipodystrophy. (2016)
  • Author(s): Kitayama N, Otsuka A, Kaku Y, Endo Y, Fujisawa A, Fujii T, Kataoka T, Hirata M, Murota H, Kabashima K.
  • Journal Title: Eur J Dermatol Volume: 26 Issue: 3 Pages: 316-317
  • DOI: 10.1684/ejd.2016.2759
  • Peer Reviewed / Open Access
• [Journal Article] Variegated RHOA mutations in adult T-cell leukemia/lymphoma (2016)
  • Author(s): Nagata Y, Kontani K, Enami T, Kataoka K, Ishii R, Totoki Y, Kataoka TR, et al.
  • Journal Title: Blood Volume: 127 Pages: 596-604
  • Peer Reviewed
• [Journal Article] Screening of BCOR-CCNB3 sarcoma using immunohistochemistry for CCNB3: A Clinicopathological Report of Three Pediatric Cases (2015)
  • Author(s): Shibayama T, Okamoto T, Nakashima Y, Kato T, Sakurai T, Minamiguchi S, Kataoka TR, Shibuya S, Yoshizawa A, Toguchida J, and Haga H
  • Journal Title: Pathol Int Volume: 65 Pages: 410-414
  • Peer Reviewed
• [Journal Article] NKp46 regulates the production of serine proteases and IL-22 in human mast cells in urticaria pigmentosa (2015)
  • Author(s): Ueshima C, Kataoka TR, Hirata M, Koyanagi I, Honda T, Tsuruyama T, Okayama Y, Seiyama A, and Haga H
  • Journal Title: Exp Dermatol Volume: 24 Pages: 675-679
  • Peer Reviewed
• [Journal Article] The killer cell Ig-like receptor 2DL4 expression in human mast cells and its potential role in breast cancer invasion (2015)
  • Author(s): Ueshima C, Kataoka TR, Hirata M, Furuhata A, Suzuki E, Toi M, Tsuruyama T, Okayama Y, and Haga H
  • Journal Title: Cancer Immunol Res Volume: 3 Pages: 871-880
  • Peer Reviewed