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Mechanisms of proliferation and metastasis of LAM cells in lymphangioleiomyomatosis (LAM)

Research Project

Project/Area Number 16590762
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionJuntendo University

Principal Investigator

SEYAMA Kuniaki  Juntendo Univ., Dept.of Respiratory Med., Lecturer, 医学部, 講師 (10226681)

Co-Investigator(Kenkyū-buntansha) KUMASAKA Toshio  Juntendo Univ., Dept.of Pathology I., Lecturer, 医学部, 講師 (00286709)
IWAKAMI Shinichiro  Juntendo Univ., Dept.of Respiratory Med., Lecturer, 医学部, 講師 (80311984)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsLymphangioleiomyomatosis / Tumor suppressor gene / Primary culture / Growth factor / Growth inhibitory factor / Estrogen / Lymphangiogenesis / リンパ腫管筋腫症
Research Abstract

Lymphangioleiomyomatosis (LAM) is a tumor-suppressor syndrome and characterized with abnormal proliferation of smooth muscle-like cells (LAM cells) in the axial lymphatics and lungs. LAM cells, a transformed cells due to the loss-of-function mutations of the TSC genes (either TSC1 or TSC2, show distinct features that LAM cells are morphorogically begin but apparently metastasize to develop new lesions along lymphatics and in the lungs. In this study, we have isolated LAM cells from various clinical specimen including surgically resected lung tissues, autopied lung tissue or lymph nodes, and chylous fluid to examine their responses to growth factors (17β-estradiol) and growth inhibitory factors (rapamycin, PDGF-R blocker, EGF-R blocker). We isolated LAM cells with several different morphorogical appearances and genetic alterations of the TSC2 gene. We consider that LAM lesions consist of several different types of LAM cells, for example, at least 2 different cells : large spindle-shaped cells with TSC2 LOH and small spindle shaped cells without TSC2 LOH. On the other hand, we identified a distinct structure, LAM cell cluster (LCC), consisting of LAM cells encompassed by a layer of lymphatic endothelial cells in chylous fluid from all of 6 different LAM patients as well as intra-LAM lesional lymphatic vessels in pathological specimen. From the in-depth immunohistochemical evaluations of axial lymphatics including thoracic duct and lymph nodes from 5 autopied cases, we presented a hypothesis that LAM-associated lymphangiogenesis fragments LAM lesion to generate and shed LCC and that LCC released into lymphatic stream is likely to be a mechanism for dissemination of LAM cells.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (28 results)

All 2005 2004

All Journal Article (24 results) Book (4 results)

  • [Journal Article] Lymphangiogenesis-Mediated Shedding of LAM Cell Clusters as a Mechanism for Dissemination in Lymphangioleiomyomatosis.2005

    • Author(s)
      Kumasaka T, Seyama K et al.
    • Journal Title

      American Journal of Surgical Pathology 29

      Pages: 1356-1366

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] 講座「画像診断」リンパ脈管筋腫症(2)-初期-2005

    • Author(s)
      佐藤輝彦, 井上恵美, 瀬山邦明
    • Journal Title

      呼吸 24

      Pages: 315-319

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 講座「画像診断」リンパ脈管筋腫症(2)-進行期-2005

    • Author(s)
      佐藤輝彦, 井上恵美, 瀬山邦明
    • Journal Title

      呼吸 24

      Pages: 320-324

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] COPDとLAM診断上の問題点2005

    • Author(s)
      井上恵美, 佐藤輝彦, 瀬山邦明
    • Journal Title

      化学療法の領域 21増刊号

      Pages: 96-104

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] リンパ脈管筋腫症(LAM)2005

    • Author(s)
      佐藤輝彦, 他
    • Journal Title

      呼吸と循環 53

      Pages: 719-727

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] LAMの遺伝子異常と病態とのかかわりをみる.分子呼吸器病2005

    • Author(s)
      瀬山邦明
    • Journal Title

      分子呼吸器病 9

      Pages: 31-37

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] 質疑応答Q&A 肺リンパ脈管筋腫症の診断、特に画像上の特徴を2005

    • Author(s)
      瀬山邦明
    • Journal Title

      日本医事新報 No.4248

      Pages: 89-90

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Lymphangiogenesis-Mediated Shedding of LAM Cell Clusters as a Mechanism for Dissemination in Lymphangioleiomyomatosis.2005

    • Author(s)
      Kumasaka T, Seyama K et al.
    • Journal Title

      Am J Surg Pathol 29

      Pages: 1356-1366

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] リンパ脈管筋腫症(LAM)2005

    • Author(s)
      佐藤輝彦 他
    • Journal Title

      呼吸と循環 53

      Pages: 719-727

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 質疑応答Q&A「肺リンパ脈管筋腫症の診断、特に画像上の特徴を」2005

    • Author(s)
      瀬山邦明
    • Journal Title

      日本医事新報 No.4248

      Pages: 89-90

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 講座「画像診断」リンパ脈管筋腫症(2)-初期-2005

    • Author(s)
      佐藤輝彦, 井上恵美, 瀬山邦明
    • Journal Title

      呼吸 (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 講座「画像診断」リンパ脈管筋腫症(2)-進行期-2005

    • Author(s)
      佐藤輝彦, 井上恵美, 瀬山邦明
    • Journal Title

      呼吸 (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] COPDとLAM診断上の問題点2005

    • Author(s)
      井上恵美, 佐藤輝彦, 瀬山邦明
    • Journal Title

      化学療法の領域 (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A patient with TSC1 germline mutation whose clinical phenotype was limited to lymphangioleiomyomatosis2004

    • Author(s)
      Sato T, Seyama K et al.
    • Journal Title

      Journal of Internal Medicine 256

      Pages: 166-173

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Lymphangiogenesis in lymphangioleiomyomatosis : its implication in the progression of lymphangioleiomyomatosis 1007-1016.2004

    • Author(s)
      Kumasaka T, Seyama K et al.
    • Journal Title

      American Journal of Surgical Pathology 28

      Pages: 1007-1016

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] リンパ脈管筋腫症2004

    • Author(s)
      瀬山邦明, 他
    • Journal Title

      家族性腫瘍 4

      Pages: 18-24

    • NAID

      10031130673

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] リンパ脈管筋腫症(LAM)2004

    • Author(s)
      佐藤輝彦, 瀬山邦明
    • Journal Title

      呼吸器科 5

      Pages: 118-126

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] リンパ脈管筋腫症とTSC遺伝子2004

    • Author(s)
      瀬山邦明, 他
    • Journal Title

      呼吸器科 6

      Pages: 457-463

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] リンパ脈管筋腫症2004

    • Author(s)
      佐藤輝彦, 瀬山邦明
    • Journal Title

      臨床放射線 49

      Pages: 9-19

    • NAID

      10031130673

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] 肺リンパ脈管筋腫症2004

    • Author(s)
      高木裕美子, 佐藤輝彦, 瀬山邦明
    • Journal Title

      COPD Frontier 3

      Pages: 33-37

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Microdissection法2004

    • Author(s)
      瀬山 邦明
    • Journal Title

      分子呼吸器病 8

      Pages: 66-69

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] 患者から医師へのシグナル."LAMって何?"から1年半2004

    • Author(s)
      瀬山 邦明
    • Journal Title

      THE LUNG perspectives 12

      Pages: 93-96

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Lymphangiogenesis in lymphangioleiomyomatosis : its implication in the progression of lymphangioleiomyomatosis 1007-1016.2004

    • Author(s)
      Kumasaka T, Seyama K et al.
    • Journal Title

      American journal of Surgical Pathology 28

      Pages: 1007-1016

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 患者から医師へのシグナル"LAMって何?"から1年半2004

    • Author(s)
      瀬山 邦明
    • Journal Title

      THE LUNG perspectives 12

      Pages: 93-96

    • Related Report
      2004 Annual Research Report
  • [Book] 今日の治療指針;肺リンパ脈管筋腫症(山口徹, 北原光夫、総編集)2005

    • Author(s)
      瀬山邦明
    • Publisher
      医学書院
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 臨床に直結する呼吸器疾患治療のエピデンス;LAMホルモン療法(長瀬隆英, 大石展也編集)2005

    • Author(s)
      瀬山邦明
    • Publisher
      文光堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 呼吸器疾患の最新の治療 2004-2006;リンパ脈管筋腫症(工藤翔二, 中田紘一郎, 貫和敏博、編集)2004

    • Author(s)
      平間未知大, 瀬山邦明
    • Publisher
      南江堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 呼吸器疾患ガイドライン 最新の診療指針 リンパ脈管筋腫症(松岡 健編集)2004

    • Author(s)
      井上恵美, 佐藤輝彦, 瀬山邦明
    • Publisher
      総合医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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