Evans Scott E, Colby Thomas V, Ryu Jay H, Limper Andrew H
Thoracic Diseases Research Unit, Division of Pulmonary & Critical Care, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Chest. 2004 Mar;125(3):1063-70. doi: 10.1378/chest.125.3.1063.
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.
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.
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.
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.
淋巴管平滑肌瘤病（LAM）是一种病因不明的罕见疾病，几乎仅影响育龄期女性，与梭形细胞增殖及受累肺组织的囊性改变有关。导致该疾病的潜在机制尚不清楚。转化生长因子（TGF）-β1是一种强效细胞因子，可促进间充质细胞增殖并调节细胞外基质（ECM）成分尤其是纤连蛋白的合成。在此，我们评估TGF-β1和基质相关纤连蛋白在显示LAM的肺标本中的表达。
从13例患者获取经证实含有病理性LAM细胞的肺活检标本。这些标本接受了针对TGF-β1、纤连蛋白以及LAM细胞典型标志物的免疫组化评估。以平行方式研究切除肿瘤周围的健康肺实质作为对照组织。
在所有13例LAM病例以及健康肺实质中，我们证实TGF-β1始终定位于气道上皮细胞。然而，在LAM组织中，在含有病理性LAM细胞的区域也始终发现有基质相关TGF-β1。值得注意的是，与LAM组织中慢性囊性区域的壁相比，在细胞高度密集区域观察到更丰富的TGF-β1。纤连蛋白是一种在活性TGF-β1作用下强烈表达的基质成分，发现在这些细胞高度密集区域与该蛋白始终共定位，支持这些区域中TGF-β1的活性。增殖LAM细胞的标志物，包括增殖细胞核抗原，在这些细胞高度密集的LAM区域也明显存在。
这些研究表明，异常LAM细胞的增殖可能与TGF-β1及相关ECM蛋白的区域表达改变有关。
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