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Molecular and clinical analysis for metastasis and invasion of cancers in small animals

Research Project

Project/Area Number 15208030
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Clinical veterinary science
Research InstitutionThe University of Tokyo

Principal Investigator

SASAKI Nobuo  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院農学生命科学研究科, 教授 (60107414)

Co-Investigator(Kenkyū-buntansha) TSUJIMOTO Hajime  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院農学生命科学研究科, 教授 (60163804)
NISHIMURA Ryohei  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院農学生命科学研究科, 教授 (80172708)
NAKAYAMA Hiroyuki  The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院農学生命科学研究科, 教授 (40155891)
MORIMATSU Masami  Hokkaido University, Graduate School of Medicine, Associate Professor, 大学院医学研究科, 助教授 (70241370)
MOCHIZUKI Manabu  The University of Tokyo, Graduate School of Agriculture and Life Sciences, Associate Professor, 大学院農学生命科学研究科, 助教授 (90261958)
小川 博之  東京大学, 大学院・農学生命科学研究科, 教授 (30012016)
Project Period (FY) 2003 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥52,390,000 (Direct Cost: ¥40,300,000、Indirect Cost: ¥12,090,000)
Fiscal Year 2006: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2005: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2004: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2003: ¥25,740,000 (Direct Cost: ¥19,800,000、Indirect Cost: ¥5,940,000)
Keywordscanine mammary tumor cell line / feline mammary tumor cell line / canine mast cell tumor / adhesion molecule / retinoid / E-cadherin / microarray / metastasis / invasion / 犬乳癌細胞株 / 猫乳癌細胞株 / sLe(X) / 細胞接着 / E-Cadherin / sLe(x) / E-cadherin / RARα / 乳癌細胞 / 肥満細胞腫細胞 / Brca2遺伝子 / CXCR4 / SDF-1 / アポトーシス
Research Abstract

In this study, we tried to analyze the mechanism of tumor metastasis and local invasion in small animals using 5 cell lines established in our laboratory.
In canine mammary cancer, expression and function of E-cadherin and catenin were compared between 4 pairs of cell lines established from the primary or metastatic lesions of the same patients. As a result, there were no differences in their expression but their function was higher in cell lines established from the metastatic lesions than those from primary lesions. This may indicate that the cells in the metastasis with low E-cadherin function are easily released from the primary lesions. In addition, sLe(x), an adhesion molecule to the endothelial cells, was alos highly expressed in one of the cell lines established from the thoracic effusion due to metastasis. Our previous data showed sLe(x) was 60% positive in the mammary tumor tissues, but not in normal mammary gland. From these data, sLe(x) may play a role in the metastasis of c … More anine mammary tumors. Currently one of this mammary tumor cells was cloned and microarray analysis was conducted to clarify the genetic change in the cells from primary and metastatic lesions in nude mice model. The result may suggest some important molecules including NfκB and hipoxia related one, which will be analyzed in the future.
In feline mammary tumors, we established 8 cell lines including 2 pairs from primary and metastatic lesions of the same patient. Using these cell lines, expression of a chemokine receptor CXCR4 and its ligand SDF-1 were compared between cell lines. Their expression was higher in those originated from metastasis than primary lesions, suggesting they may also play a role in tumor metastasis in feline mammary tumors. In addition, tumor-suppressing molecule, Braca2, was also analyzed in relation to the malignancy of this tumor.
Retinoids, vitamin A derivatives, may control the growth of canine mast cell tumors. This tumor growth-inhibitory effect of retinoids against canine mast cell tumors was mediated by a receptor RAR alpha and via inducing apoptosis in both in vitro model and in vivo nude mice model, as in human acute promyelocytic leukemia. These results suggest the retinoids may be a potential chemotherapeutic agent for canine mast cell tumors. For canine osteosarcoma, gene therapy using wild type p53 transfection using adenovirus as a vector virus. This trial showed some efficacy in nude mice model and even in the canine patients with ostesarcoma. For canine melanoma, spindle check point function is currently investigated to analyze its relationship to chemotherapeutic response of the tumor. Less

Report

(5 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (36 results)

All 2007 2006 2005 2004 2003 Other

All Journal Article (34 results) Publications (2 results)

  • [Journal Article] Expression and subcellular localization of E-cadherin, alpha-catenin, and beta-catenin in 8 feline mammary tumor cell lines2007

    • Author(s)
      Takauji, S., Watanabe, M., Uyama, R., et al.
    • Journal Title

      J. Vet. Med. Sci. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression and subcellular localization of E-cadherin, alpha-catenin, and beta-catenin in 8 feline mammary tumor cell lines2007

    • Author(s)
      Takauji, S., Watanabe, M., Uyama, R., et al.
    • Journal Title

      J.Vet.Med.Sci. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Expression and subcellular localization of E-catenin, α-catenin, and β-catenin in 8 feline mammary tumor cell lines2007

    • Author(s)
      Takauji, S., Watanabe, M., Sasaki, N., et al.
    • Journal Title

      J. Vet. Med. Sci. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cyclopedic protein expression analysis of cultured canine mammary gland adenocarcinoma cells from six tumours2006

    • Author(s)
      Nakagawa, T., Watanabe, M., Ohashi, E., et al.
    • Journal Title

      Res. Vet. Sci. 80

      Pages: 317-323

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Relationship between retinoic acid receptor alpha gene expression and growth-inhibitory effect of all-trans retinoic acid on canine tumor cells2006

    • Author(s)
      Miyajima, N., Watanabe, M., Ohashi, E., et al.
    • Journal Title

      J. Vet. Intern. Med. 20

      Pages: 348-354

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Retinoids induce growth inhibition and apoptosis in mast cell tumor cell lines2006

    • Author(s)
      Ohashi, E., Miyajima, N., Nakagawa, T., et al.
    • Journal Title

      J. Vet. Med. Sci. 68

      Pages: 797-802

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Establishment of four pairs of canine mammary tumour cell lines derived from primary and metastatic origin and their E-cadherin expression2006

    • Author(s)
      Uyama, R., Nakagawa, T., Hong, S-H., et al.
    • Journal Title

      Vet. Comp. Oncol. 4

      Pages: 104-113

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cyclopedic protein expression analysis of cultured canine mammary gland adenocarcinoma cells from six tumours2006

    • Author(s)
      Nakagawa, T., Watanabe, M., Ohashi, E., et al.
    • Journal Title

      Res.Vet.Sci. 80

      Pages: 317-323

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Relationship between retinoic acid receptor alpha gene expression and growth-inhibitory effect of all-trans retinoic acid on canine tumor cells2006

    • Author(s)
      Miyajima, N., Watanabe, M., Ohashi, E., et al.
    • Journal Title

      J.Vet.Intern.Med. 20

      Pages: 348-354

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Retinoids induce growth inhibition and apoptosis in mast cell tumor cell lines2006

    • Author(s)
      Ohashi, E., Miyajima, N., Nakagawa, T., et al.
    • Journal Title

      J.Vet.Med.Sci. 68

      Pages: 797-802

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Establishment of four pairs of canine mammary tumour cell lines derived from primary and metastatic origin and their E-cadherin expression2006

    • Author(s)
      Uyama, R., Nakagawa, T., Hong, S-H., et al.
    • Journal Title

      Vet.Comp.Oncol. 4

      Pages: 104-113

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Retinoids induce growth inhibition and apoptosis in mast cell tumor cell lines2006

    • Author(s)
      Ohashi, E.Miyajima, N., Sasaki, N.eral.
    • Journal Title

      J. Vet. Med. Sci. 68

      Pages: 797-802

    • NAID

      130000447777

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Establishment of four pairs of canine mammary tumour cell lines derived from primary and metastatic origin and their E-cadherin expression2006

    • Author(s)
      Uyama, R., Nakagawa, T., Sasaki, N., et al.
    • Journal Title

      Vet. Comp. Oncol. 4

      Pages: 104-113

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cyclopedic protein expression analysis of cultured canine mammary gland adenocarcinoma cells from six tumours2006

    • Author(s)
      Nakagawa, T, Watanabe, M, Sasaki, N et al.
    • Journal Title

      Res Vet Sci 80

      Pages: 317-323

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Relationship between retinoic acid receptor alpha gene expression and growth-inhibitory effect of all-tarns retinoic acid on canine tumor cells2006

    • Author(s)
      Miyajima, N, Watanabe, M, Sasaki, N et al.
    • Journal Title

      J Vet Intern Med (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Identification and characterization of a canine highly similar to retinoic acid receptor alpha2005

    • Author(s)
      Miyajima, N., Watanabe, M., Ohashi, E., et al.
    • Journal Title

      DNA Sequence 16

      Pages: 7-15

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Insertion/deletion polymorphism in the Braca 2 nuclear localization signal2005

    • Author(s)
      Yasunaga, Y., Morimatsu, M., Ochiai, K., et al.
    • Journal Title

      Biomed. Res. 26

      Pages: 109-115

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Establishment and characterization of eight feline mammary adenocarcinoma cell lines2005

    • Author(s)
      Uyama, R., Hong, S-H, Nakagawa, T., et al.
    • Journal Title

      J. Vet. Med. Sci. 67

      Pages: 1273-1276

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Analysis of genetic variations in the exon 27 region of canine Braca 2 locus2005

    • Author(s)
      Yoshikawa, Y., Morimatsu, M., Ochiai, K., et al.
    • Journal Title

      J. Vet. Med. Sci. 67

      Pages: 1013-1017

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Insertion/deletion polymorphism in the Braca 2 nuclear localization signal2005

    • Author(s)
      Yasunaga, Y., Morimatsu, M., Ochiai, K., et al.
    • Journal Title

      Biomed.Res. 26

      Pages: 109-115

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Establishment and characterization of eight feline mammary adenocarcinoma cell lines2005

    • Author(s)
      Uyama, R., Hong, S-H, Nakagawa, T., et al.
    • Journal Title

      J.Vet.Med.Sci. 67

      Pages: 1273-1276

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Analysis of genetic variations in the exon 27 region of canine Braca 2 locus2005

    • Author(s)
      Yoshikawa, Y., Morimatsu, M., Ochiai, K., et al.
    • Journal Title

      J.Vet.Med/Sci. 67

      Pages: 1013-1017

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Identification and characterization of a canine highly similar to retinoic acid receptor alpha2005

    • Author(s)
      Miyajima, M, Nishimura, R, Sasaki, N, et al.
    • Journal Title

      DNA Sequence 16

      Pages: 7-15

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Insertion/deletion polymorphism in the BRCA2 nuclear localization signal2005

    • Author(s)
      Yasunaga, Y, Morimatsu, M, Sasaki, N, Hashizume, K et al.
    • Journal Title

      Biomed Res 26

      Pages: 109-116

    • NAID

      130004470639

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Establishment of eight feline mammary adenocarcinoma cell lines2005

    • Author(s)
      Uyama, R, Mochizuki, M, Nishimura, R, Sasaki, N et al.
    • Journal Title

      J Vet Med Sci 67

      Pages: 1272-1276

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Analysis of genetic variations in the exon 27 region of the canine BRCA2 locus2005

    • Author(s)
      Yoshikawa, Y, Morimatsu, M, Hashizume, K, Sasaki, N et al.
    • Journal Title

      J Vet Med Sci 67

      Pages: 1013-1017

    • NAID

      110003983121

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Molecular cloning of a canine HS-RARα2005

    • Author(s)
      Miyajima, N., Sasaki, N., et al.
    • Journal Title

      DNA Sequence (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Establishment and characterization of four melanoma cell line2004

    • Author(s)
      Inoue, K., Ohashi, E., Kadosawa, T., et al.
    • Journal Title

      J. Vet. Med. Sci. 66

      Pages: 1437-1440

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Establishment and characterization of four melanoma cell line2004

    • Author(s)
      Inoue, K., Ohashi, E., Kadosawa, T., et al.
    • Journal Title

      J.Vet.Med.Sci. 66

      Pages: 1437-1440

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Establishment and characterization of four Canine melanoma Cell lines2004

    • Author(s)
      Inoue, K., Ohashi., E.et al.
    • Journal Title

      J Vet Med Sci 66

      Pages: 1473-1440

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Role of CXCR4 and SDF-1 in mammary tumor metastasis in the cat.2003

    • Author(s)
      Oonuma, T., Morimatsu, M, et al.
    • Journal Title

      J. Vet. Med. Sci. 65

      Pages: 1069-1073

    • NAID

      110003886128

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Properties of the tumor suppressor gene Braca 2 in the cat.2003

    • Author(s)
      Oonuma, T., Morimatsu, M., Ochiai, K., et al.
    • Journal Title

      J. Vet. Med. Sci. 65

      Pages: 1123-1126

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Role of CXCR4 and SDF-1 in mammary tumor metastasis in the cat2003

    • Author(s)
      Oonuma, T., Morimatsu, M, et al.
    • Journal Title

      J.Vet.Med.Sci. 65

      Pages: 1069-1073

    • NAID

      110003886128

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Properties of the tumor suppressor gene Braca 2 in the cat.2003

    • Author(s)
      Oonuma, T., Morimatsu, M., Ochiai, K., et al.
    • Journal Title

      J.Vet.Med.Sci. 65

      Pages: 1123-1126

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Publications] Oonuma T, Morimatsu M et al.: "Properties of the tumor suppressor gene Brca2 in the cat"J Vet Med Sci. 65. 1123-1126 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Oonuma T, Morimatsu M et al.: "Role of CXCR4 and SDF-1 in mammary tumor metastasis in the cat"J Vet Med Sci. 65. 1069-1073 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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