Vascular endothelial growth factor is increased in ascites from metastatic pancreatic cancer.
BACKGROUND
Vascular endothelial growth factor (VEGF) is an angiogenic factor that increases vascular permeability. VEGF stimulates capillary formation and has mitogenic effects on vascular endothelial cells. The development of malignant ascites causes significant morbidity. We hypothesized that increased levels of VEGF play a role in the development of malignant ascites in patients with pancreatic cancer.


METHODS
Athymic mice underwent orthotopic implantation of human pancreatic ductal adenocarcinoma tumors (250,000 cells) into the body of the pancreas. Tumors were allowed to grow for 12 weeks, at which time ascites develops in 50% of mice. Paracentesis was performed on mice with noticeable ascites. Saline lavage was performed in mice with equivalent pancreatic tumor masses without ascites and served as control. Both ascites and tumor masses were harvested for VEGF protein quantitation by ELISA.


RESULTS
VEGF protein levels were elevated in malignant ascites by 15-fold compared to control mice with equivalent tumors (N = 6, P < 0.001, t test). VEGF levels were slightly higher in the primary tumor masses harvested from mice without ascites. Mice with ascites also had metastatic nodules throughout the abdominal cavity.


CONCLUSIONS
We are reporting for the first time that VEGF levels are increased in the ascites of nude mice with orthotopically transplanted human pancreatic cancers. VEGF increases vascular permeability and allows for extrapancreatic seeding of tumors. Irrespective of primary tumor size, intraperitoneal VEGF levels are increased when ascites and extrapancreatic nodules are present, while a paradoxical decrease is observed in VEGF levels of primary tumors.
Liu
Carson D
CD
West Los Angeles Veterans Administration Medical Center, Los Angeles, California, USA.
Tilch
Lloyd
L
Kwan
David
D
McFadden
David W
DW
D000818:Animals; D001201:Ascites / Q000378:metabolism*; D001202:Ascitic Fluid / Q000737:chemistry; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry / Q000503:physiopathology*; D016228:Endothelial Growth Factors / Q000032:analysis* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008222:Lymphokines / Q000032:analysis* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000503:physiopathology*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors