Published ahead of print on June 23, 2005, doi:10.1164/rccm.200504-615OC
© 2005 American Thoracic Society doi: 10.1164/rccm.200504-615OC Lung Adenocarcinoma Global Profiling Identifies Type II Transforming Growth Factor-ß Receptor as a Repressor of InvasivenessDepartments of Pathology, Medicine, and Biomedical Informatics, and Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York Correspondence and requests for reprints should be addressed to Charles A. Powell, M.D., Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Medical Center, 630 West 168th Street, Box 91, New York, New York. E-mail: cap6{at}columbia.edu Rationale: Lung adenocarcinoma histology and clinical outcome are heterogeneous and associated with tumor invasiveness. Objectives: We hypothesized that invasiveness is associated with a distinct molecular signature and that genes differentially expressed in tumor or adjacent stroma will identify cell surface signal transduction and matrix remodeling pathways associated with the acquisition of invasiveness in lung adenocarcinoma. Main Results: Microarray analysis of microdissected noninvasive bronchioloalveolar carcinoma (BAC) and invasive adenocarcinoma and adenocarcinoma-mixed type with BAC features identified transcriptional profiles of lung adenocarcinoma invasiveness. Among the signature set that was lower in adenocarcinoma-mixed compared with BAC was the type II transforming growth factor ß (TGF-ß) receptor, suggesting downregulation of TGFßRII is an early event in lung adenocarcinoma metastasis. Immunostaining in independently acquired specimens demonstrated a correlation between TßRII expression and length of tumor invasion. Repression of TGFßRII in lung cancer cells increased tumor cell invasiveness and activated p38 mitogen-activated protein kinases. Microarray analysis of invasive cells identified potential downstream mediators of TGFßRII with differential expression in lung adenocarcinomas. Conclusions: The repression of type II TGF-ß receptor may act as a significant determinant of lung adenocarcinoma invasiveness, an early step in tumor progression toward metastasis.
Key Words: adenocarcinoma • lung cancer • microarray analysis • neoplasm invasiveness • transforming growth factor-ß This article has been cited by other articles:
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