title: Pleural mesothelial cell (PMC) defense mechanisms against malignancy.
abstract: Tumors such as ovarian, lung, and breast have been found to have a predilection for the pleura. Pleural mesothelial cells (PMCs) play an active role in pleural inflammation via release of cytokines. However, mechanisms whereby PMCs defend themselves against invading malignant cells are unknown. In the present study, we hypothesized that PMCs release the antiangiogenic factor endostatin and inhibit malignant cell invasion. We evaluated the endostatin levels in malignant (MAL) and congestive heart failure (CHF) pleural fluids (PF). Endostatin expression by PMC was also demonstrated by Western analysis and confocal microscopy. Our results demonstrate that CHF PF contained significantly higher levels of endostatin when compared with MAL PF. PMCs alone released a significantly greater amount of endostatin when compared with ovarian cancer cells (OCCs). When the PMC were cocultured with OCCs without contact, there was an increase in the endostatin production. However, when the PMCs were cocultured in direct contact with OCCs the endostatin levels significantly decreased. Endostatin production was upregulated in the presence of tumor cells but not when OCCs were adherent to underlying PMC monolayer. Immunofluorescent staining of PMCs for endostatin correlated with endostatin release. These findings suggest that PMCs play a key role in the antiangiogenesis process by producing endostatin in the pleural space, and thus preventing tumor spread and metastasis in the pleura.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Veterans Affairs Medical Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Najmunnisa
authors.initials: N
authors.lastname: Nasreen
authors.forename: Kamal A
authors.initials: KA
authors.lastname: Mohammed
authors.forename: Kerry
authors.initials: K
authors.lastname: Sanders
authors.forename: Joyce
authors.initials: J
authors.lastname: Hardwick
authors.forename: Robert D
authors.initials: RD
authors.lastname: Van Horn
authors.forename: P S
authors.initials: PS
authors.lastname: Sriram
authors.forename: Carlos
authors.initials: C
authors.lastname: Ramirez-Icaza
authors.forename: Chadi
authors.initials: C
authors.lastname: Hage
authors.forename: Veena B
authors.initials: VB
authors.lastname: Antony
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D043169:Endostatins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D010994:Pleura / Q000166:cytology / Q000378:metabolism* / Q000473:pathology
chemical_list: D043169:Endostatins