| Project/Area Number |
16590762
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Juntendo University |
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Principal Investigator |
SEYAMA Kuniaki Juntendo Univ., Dept.of Respiratory Med., Lecturer, 医学部, 講師 (10226681)
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| 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)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| 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)
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| Keywords | Lymphangioleiomyomatosis / Tumor suppressor gene / Primary culture / Growth factor / Growth inhibitory factor / Estrogen / Lymphangiogenesis / リンパ腫管筋腫症 |
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| 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.
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