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Transforming growth factor-beta 1 and extracellular matrix-associated fibronectin expression in pulmonary lymphangioleiomyomatosis.
- Source :
-
Chest [Chest] 2004 Mar; Vol. 125 (3), pp. 1063-70. - Publication Year :
- 2004
-
Abstract
- Study Objectives: Lymphangioleiomyomatosis (LAM) is a rare disorder of unknown etiology, affecting almost exclusively women of childbearing age, that is associated with the proliferation of spindle cells and cystic changes in the affected lung. The underlying processes that contribute to this disease are poorly understood. Transforming growth factor (TGF)-beta(1) is a potent cytokine that promotes mesenchymal cell proliferation and regulates the synthesis of extracellular matrix (ECM) components, particularly fibronectins. Herein, we evaluate the expression of TGF beta(1) and matrix-associated fibronectin in lung specimens demonstrating LAM.<br />Design: Lung biopsy specimens that were confirmed to contain pathologic LAM cells were obtained from 13 patients. The specimens were submitted to immunohistochemical evaluation for TGF beta(1) and fibronectin, as well as the typical markers of LAM cells. Healthy lung parenchyma surrounding resected neoplasms was studied in a parallel fashion as control tissues.<br />Measurements and Results: In all 13 LAM cases and in healthy lung parenchyma, we demonstrated that TGF beta(1) localized consistently to airway epithelial cells. However, in LAM tissues, matrix-associated TGF beta(1) was also consistently found in regions containing pathologic LAM cells. Notably, more abundant TGF beta(1) was observed in highly cellular areas compared to the walls of chronic cystic regions in LAM tissues. Fibronectin, a matrix component that is strongly expressed in response to active TGF beta(1) was found to consistently colocalize with this protein in these highly cellular regions, supporting TGF beta(1) activity in these regions. The markers of proliferating LAM cells, including proliferating cell nuclear antigen, were also markedly present in these highly cellular LAM regions.<br />Conclusion: These studies suggest that the proliferation of aberrant LAM cells may be associated with altered regional expression of TGF beta(1) and related ECM proteins.
- Subjects :
- Actins analysis
Adult
Antigens, Neoplasm
Biomarkers analysis
Extracellular Matrix metabolism
Female
Humans
Immunohistochemistry
Lung Neoplasms diagnosis
Lung Neoplasms pathology
Lymphangioleiomyomatosis diagnosis
Lymphangioleiomyomatosis pathology
Melanoma-Specific Antigens
Middle Aged
Neoplasm Proteins analysis
Proliferating Cell Nuclear Antigen analysis
Respiratory Mucosa metabolism
Transforming Growth Factor beta1
Fibronectins metabolism
Lung metabolism
Lung Neoplasms metabolism
Lymphangioleiomyomatosis metabolism
Transforming Growth Factor beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0012-3692
- Volume :
- 125
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Chest
- Publication Type :
- Academic Journal
- Accession number :
- 15006970
- Full Text :
- https://doi.org/10.1378/chest.125.3.1063