Role for activation of matrix metalloproteinases in the pathogenesis of pulmonary lymphangioleiomyomatosis

Arch Pathol Lab Med. 2000 Feb;124(2):267-75. doi: 10.5858/2000-124-0267-RFAOMM.


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.

MeSH terms

  • Actins / metabolism
  • Adult
  • Antigens, Neoplasm
  • Enzyme Activation
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / pathology
  • Lymphangioleiomyomatosis / enzymology*
  • Lymphangioleiomyomatosis / pathology
  • Matrix Metalloproteinases / metabolism*
  • Melanoma-Specific Antigens
  • Microscopy, Confocal
  • Middle Aged
  • Muscle, Smooth / enzymology
  • Neoplasm Proteins / metabolism
  • Proliferating Cell Nuclear Antigen / metabolism


  • Actins
  • Antigens, Neoplasm
  • Melanoma-Specific Antigens
  • Neoplasm Proteins
  • Proliferating Cell Nuclear Antigen
  • Matrix Metalloproteinases