title: Role for activation of matrix metalloproteinases in the pathogenesis of pulmonary lymphangioleiomyomatosis.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs) have been shown to be involved in the pathogenesis of the destructive pulmonary lesions in patients with lymphangioleiomyomatosis (LAM); in the present report, the activation of these enzymes is examined.
  
  
  OBJECTIVE
  To evaluate the role of MMPs and their activating enzymes, immunohistochemical and confocalmicroscopic techniques were used to localize alpha-smooth muscle actin (alpha-SMA), HMB-45, proliferating cell nuclear antigen (PCNA), MMP-2, membrane-type 1 MMP (MT1-MMP), MT2-MMP, and MT3-MMP in lung tissues from 10 women with LAM. Tissue samples were obtained from 5 patients before treatment and in 5 patients after hormone treatment (progesterone and/or tamoxifen citrate).
  
  
  RESULTS
  Staining for alpha-SMA and MMP-2 was present in all the abnormal smooth muscle cells (LAM cells) in both groups. The percentages of PCNA-, MMP-2-, or MT1-MMP-positive LAM cells were much higher in the untreated group than in the treated group, whereas the percentages of HMB-45-reactive LAM cells were similar in both groups. The reactions for MT1-MMP and PCNA were preferentially localized in small spindle-shaped LAM cells; the reaction for HMB-45 was found in large epithelioid LAM cells. Many of the PCNA-positive cells were also positive for MT1-MMP. Staining for MT2-MMP and MT3-MMP was negative.
  
  
  CONCLUSIONS
  This study demonstrates an association between cellular proliferation and the presence of MT1-MMP in LAM cells. The activation of MMP-2 by MT1-MMP may play an important role in the destruction of lung tissue in this disorder.
authors.affiliation: Pathology Section, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: K
authors.initials: K
authors.lastname: Matsui
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.forename: Z X
authors.initials: ZX
authors.lastname: Yu
authors.forename: W D
authors.initials: WD
authors.lastname: Travis
authors.forename: J
authors.initials: J
authors.lastname: Moss
authors.forename: V J
authors.initials: VJ
authors.lastname: Ferrans
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000951:Antigens, Neoplasm; D004789:Enzyme Activation; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D018192:Lymphangioleiomyomatosis / Q000201:enzymology* / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D058950:Melanoma-Specific Antigens; D018613:Microscopy, Confocal; D008875:Middle Aged; D009130:Muscle, Smooth / Q000201:enzymology; D009363:Neoplasm Proteins / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
chemical_list: D000199:Actins; D000951:Antigens, Neoplasm; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D020782:Matrix Metalloproteinases