Document Detail

Ovarian carcinoma cells and IL-1beta-activated human peritoneal mesothelial cells are possible sources of vascular endothelial growth factor in inflammatory and malignant peritoneal effusions.
MedLine Citation:
PMID:  15943987     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Inflammatory or malignant peritoneal diseases are associated with high levels of ascitic vascular endothelial growth factor (VEGF). We compared the VEGF secretion by human peritoneal mesothelial cells (HPMC) and ovarian carcinoma (OVCA) cells and its regulation by pro-inflammatory cytokines. MATERIALS AND METHODS: VEGF secretion in cultured HPMC, established human OVCA cell lines, and inflammatory or OVCA-associated ascites was determined by enzyme linked immunosorbent assay. RESULTS: HPMC constitutively produced VEGF at median levels of 43 +/- 7 pg/10(5) cells. Treatment of HPMC with 1 ng/ml IL-1beta (567 +/- 213 pg/10(5) cells) or TNF-alpha (89 +/- 1 pg/10(5) cells) resulted in a 13-fold (P < 0.01) or 2-fold (P < 0.05) elevation of the VEGF secretion. In OVCA, the constitutive VEGF expression was 8-fold higher than VEGF levels in HPMC (364 +/- 185 pg/10(5) cells; P < 0.001). VEGF secretion in OVCA cells was also increased by IL-1beta (514 +/- 105 pg/10(5) cells; P < 0.01) or TNF-alpha (458 +/- 168 pg/10(5) cells; P < 0.01) reaching similar levels as in IL-1beta-activated HPMC. Median VEGF levels in malignant ascites (2761 +/- 1549 pg/ml) were 11-fold higher compared with levels in inflammatory fluids (244 +/- 170 pg/ml; P < 0.01). VEGF levels in both inflammatory- and OVCA-associated fluids correlated with ascitic IL-1beta levels (P < 0.05). CONCLUSION: We identified ovarian cancer cells and/or IL-1beta-activated peritoneal mesothelial cells as important sources of ascitic VEGF. The present data indicate that IL-1beta-triggered VEGF production by neoplastic and normal cells is a common pathomechanism for ascites formation in both inflammatory and malignant conditions.
Sylvia Stadlmann; Albert Amberger; Juergen Pollheimer; Guenther Gastl; Felix Albert Offner; Raimund Margreiter; Alain Gustave Zeimet
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Gynecologic oncology     Volume:  97     ISSN:  0090-8258     ISO Abbreviation:  Gynecol. Oncol.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-06-09     Completed Date:  2005-08-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0365304     Medline TA:  Gynecol Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  784-9     Citation Subset:  IM    
Department of Pathological Anatomy, Innsbruck Medical University, A-6020 Innsbruck, Austria.
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MeSH Terms
Ascitic Fluid / metabolism,  pathology,  secretion
Cell Line, Tumor
Epithelial Cells / metabolism,  secretion*
Interleukin-1 / metabolism,  pharmacology*
Ovarian Neoplasms / metabolism,  pathology,  secretion*
Peritoneal Cavity / cytology
Peritonitis / metabolism*,  pathology
Recombinant Proteins / pharmacology
Secretory Rate / drug effects
Vascular Endothelial Growth Factor A / biosynthesis,  secretion*
Reg. No./Substance:
0/Interleukin-1; 0/Recombinant Proteins; 0/Vascular Endothelial Growth Factor A

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