title: A Model of Lymphangioleiomyomatosis in a Three-Dimensional Culture System.
abstract: BACKGROUND
  Lymphangioleiomyomatosis (LAM) is a tumor consisting of benign-looking neoplastic cells, but its wretched clinical outcome often resembles a malignant disease. LAM cell clusters (LCCs), unique microstructures commonly found in LAM-associated chylous effusion, are aggregates of LAM cells rimmed by lymphatic endothelium. LCCs seem to be crucial participants in the dissemination and progression of LAM.
  
  
  RESULTS
  LCCs isolated from LAM-associated chylous effusion were embedded in a three-dimensional (3-D) culture gels, and then placed in a humidified CO2 incubator. During serial observations of their morphological changes, we found tube formations with lymphatic endothelial cells when LCCs settled side by side in 3-D gels. On the other hand, when LCCs were embedded separately enough to be isolated at their initial sites of settlement in the gels, each of LCCs gradually broke down, leaving a "cyst-like" hole after 7 days at the site where LCCs initially resided. Finally, we demonstrated that "cyst-like" hole formation in 3-D gels was inhibited with treatment with doxycycline or recombinant human VEGF receptor-3.
  
  
  CONCLUSIONS
  We consider that our observation of this sequence in vitro illustrates how LCCs behave in vivo while enacting their important role in the progression of LAM. Our results indicate that the 3-D gel culture system for LCCs is a useful tool for exploring the effects of new therapeutic drugs under conditions when LCCs are constantly available.
authors.affiliation: 1 Department of Pathology, Japanese Red Cross Medical Center , Tokyo, Japan .|5 The Study Group of Pneumothorax and Cystic Lung Diseases , Tokyo, Japan .
authors.forename: Toshio
authors.initials: T
authors.lastname: Kumasaka
authors.affiliation: 2 Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine , Tokyo, Japan .|5 The Study Group of Pneumothorax and Cystic Lung Diseases , Tokyo, Japan .
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Hoshika
authors.affiliation: 2 Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine , Tokyo, Japan .|5 The Study Group of Pneumothorax and Cystic Lung Diseases , Tokyo, Japan .
authors.forename: Etsuko
authors.initials: E
authors.lastname: Kobayashi
authors.affiliation: 3 Division of Human Pathology, Juntendo University Faculty of Medicine and Graduate School of Medicine , Tokyo, Japan .|5 The Study Group of Pneumothorax and Cystic Lung Diseases , Tokyo, Japan .
authors.forename: Keiko
authors.initials: K
authors.lastname: Mitani
authors.affiliation: 2 Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine , Tokyo, Japan .|5 The Study Group of Pneumothorax and Cystic Lung Diseases , Tokyo, Japan .
authors.forename: Makiko K
authors.initials: MK
authors.lastname: Okura
authors.affiliation: 4 Departments of Surgery and Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California , California.
authors.forename: Young Kwon
authors.initials: YK
authors.lastname: Hong
authors.affiliation: 2 Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine , Tokyo, Japan .
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: 2 Division of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine , Tokyo, Japan .|5 The Study Group of Pneumothorax and Cystic Lung Diseases , Tokyo, Japan .
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Seyama
mesh_terms: D018929:Cell Culture Techniques; D006801:Humans; D018192:Lymphangioleiomyomatosis / Q000473:pathology*; D008954:Models, Biological