Matrix metalloproteinases and tissue inhibitors of metalloproteinases in bronchial squamous preinvasive lesions

Françoise B. Galateau-Salle, Rafael E. Luna, Koji Horiba, Mary N. Sheppard, Tomayoshi Hayashi, Marian V. Fleming, Thomas V. Colby, William Bennett, Curtis C. Harris, William G. Stetler-Stevenson, Lance Liotta, Victor J. Ferrans, William D. Travis

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Metalloproteinases and their inhibitors are known to play an important role in the extracellular matrix remodeling associated with preinvasive lesions and invasive carcinomas; however, little is known about their role in early lung carcinoma. Immunohistochemical studies were made of the reactivity of bronchial squamous preneoplastic lesions from cigarette smokers, including basal cell hyperplasia, squamous metaplasia, dysplasia, carcinoma in situ, and invasive squamous cell carcinoma for matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and type IV collagen in 13 patients. Staining for type IV collagen disclosed discontinuities in basement membranes from basal cell hyperplasia to dysplasia, progressing to destruction in carcinoma in situ and invasive carcinoma. Reactivity for MMP-9 was mild in basal cell hyperplasia and squamous metaplasia, increasing in carcinoma in situ and invasive carcinoma. In contrast, reactivity for MMP-1 was strong in basal cell hyperplasia and squamous metaplasia, decreasing in carcinoma in situ and invasive carcinoma. Some neoplastic cells in carcinoma in situ and invasive carcinoma were MMP-3 positive. Staining for MMP-2 and TIMP-1 was moderate to strong in all squamous preinvasive lesions. Confocal microscopy showed MMP-9-positive cells passing through fragmented basement membranes in which type IV collagen and MMP-9 were colocalized. Type IV collagen colocalized with MMP-2 in all lesions and with TIMP-1 in basal cell hyperplasia and squamous metaplasia. The inverse relationships between the reactivity for MMP-1 and MMP-9 with progression of bronchial squamous preinvasive lesions suggest important roles for these MMPs in basement membrane remodeling in these lesions.

Original languageEnglish (US)
Pages (from-to)296-305
Number of pages10
JournalHuman Pathology
Volume31
Issue number3
DOIs
StatePublished - Jan 1 2000

Keywords

  • Basal cell hyperplasia
  • Bronchus
  • Carcinoma in situ
  • Lung
  • Lung cancer
  • Metalloproteinase
  • Squamous dysplasia
  • Squamous metaplasia
  • Tissue inhibitor of metalloproteinase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Galateau-Salle, F. B., Luna, R. E., Horiba, K., Sheppard, M. N., Hayashi, T., Fleming, M. V., Colby, T. V., Bennett, W., Harris, C. C., Stetler-Stevenson, W. G., Liotta, L., Ferrans, V. J., & Travis, W. D. (2000). Matrix metalloproteinases and tissue inhibitors of metalloproteinases in bronchial squamous preinvasive lesions. Human Pathology, 31(3), 296-305. https://doi.org/10.1016/S0046-8177(00)80242-7