Document Detail

Development of a Lymphangioleiomyomatosis Model by Endonasal Administration of Human TSC2(-/-) Smooth Muscle Cells in Mice.
MedLine Citation:
PMID:  22770663     Owner:  NLM     Status:  Publisher    
Lymphangioleiomyomatosis (LAM) is an interstitial lung disease characterized by invasion and proliferation of abnormal smooth muscle (ASM) cells in lung parenchyma and axial lymphatics. LAM cells bear mutations in tuberous sclerosis (TSC) genes. TSC2(-/-) ASM cells, derived from a human renal angiomyolipoma, require epidermal growth factor (EGF) for proliferation. Blockade of EGF receptors (EGFR) causes cell death. TSC2(-/-) ASM cells, previously labeled with PKH26-GL dye, were endonasally administered to 5-week-old immunodeficient female nude mice, and 4 or 26 weeks later anti-EGFR antibody or rapamycin was administered twice a week for 4 consecutive weeks. TSC2(-/-) ASM cells infiltrated lymph nodes and alveolar lung walls, causing progressive destruction of parenchyma. Parenchymal destruction was efficiently reversed by anti-EGFR treatment and partially by rapamycin treatment. Following TSC2(-/-) ASM cell administration, lymphangiogenesis increased in lungs as indicated by more diffuse LYVE1 expression and high murine VEGF levels. Anti-EGFR antibody and rapamycin blocked the increase in lymphatic vessels. This study shows that TSC2(-/-) ASM cells can migrate and invade lungs and lymph nodes, and anti-EGFR antibody is more effective than rapamycin in promoting lung repair and reducing lymphangiogenesis. The development of a model to study metastasis by TSC cells will also help to explain how they invade different tissues and metastasize to the lung.
Elena Lesma; Eloisa Chiaramonte; Eleonora Isaia; Vera Grande; Silvia Ancona; Emanuela Orpianesi; Anna Maria Di Giulio; Alfredo Gorio
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-3
Journal Detail:
Title:  The American journal of pathology     Volume:  -     ISSN:  1525-2191     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Laboratory of Pharmacology, Department of Medicine, Surgery and Dentistry, Polo H. San Paolo, Faculty of Medicine and Surgery, University of Milan, Milan, Italy.
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