Eur Respir J 2007, doi:10.1183/09031936.00061606
Talc mediates angiostasis in malignant pleural effusions via endostatin induction
1 Division of Pulmonary and Critical Care Medicine, Dept of Medicine, College of Medicine, University of Florida, PO Box 100225,Gainesville, FL 32610-0225
* To whom correspondence should be addressed. E-mail: antonvb{at}medicine.ufl.edu.
Talc remains the most effective sclerosing agent for pleurodesis. However, its mechanism of action in resolving pleural malignant disease remains unclear. The present study evaluated the angiogenic balance in the pleural space in patients with malignant pleural effusions (MPE) following talc insufflation. Patient pleural fluid samples were collected both before and after talc insufflation. In vitro, the ability of pleural mesothelial cells (PMC) and malignant mesothelioma cells (MMC) to produce endostatin was compared. The biological effects of pleural fluids and conditioned media from talc activated PMC on endothelial cells were evaluated by performing proliferation, invasion, tube formation and apoptosis assays. Pleural fluids from patients with MPE who received thoracoscopic talc insufflation contained significantly higher levels of endostatin (median: 16.75 ng·ml-1; p<0.001) compared to pre talc instillation (median: 1.06 ng·ml-1). Talc activated PMC released significantly greater amounts of endostatin (1052.39±38.66 pg·ml-1; P<0.001) when compared to a MMC line (134.73±8.72 pg·ml-1). We conclude that talc alters the angiogenic balance in pleural space from a biologically active, angiogenic environment to an angiostatic milieu. Functional improvement following talc poudrage in patients with malignant pleural effusions may in part, reflect these alterations in the pleural space. Keywords: Angiogenesis, malignant pleural effusions, pleura, pleurodesis
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