Markedly elevated levels of vascular endothelial growth factor in malignant ascites

Brian K. Zebrowski, Wenbiao Liu, Karen Ramirez, Yoshito Akagi, Gordon Mills, Lee M. Ellis

Research output: Contribution to journalArticle

208 Citations (Scopus)

Abstract

Background: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that also has the ability to increase vascular permeability. Malignant ascites has significant morbidity, but the mechanism of its development is unknown. Because of the permeability-inducing properties of VEGF, we hypothesized that malignant ascites formation is associated with high levels of VEGF. The purpose of our study was to determine the role of VEGF in malignant ascites formation. Methods: Ascites from 25 patients with gastric (n = 6), colon (n = 7), or ovarian (n = 12) cancers was collected by paracentesis or surgery. VEGF protein levels were determined by enzyme-linked immunosorbent assay. The effect of ascites on endothelial cell permeability was assessed by evaluating propidium iodide uptake by human umbilical vein endothelial cells (HUVECs) exposed to ascites. Neutralizing antibodies to VEGF added to ascites were used to determine the causal effect of VEGF in permeability induction. Results: VEGF protein levels were markedly increased in malignant ascites compared with levels in nonmalignant cirrhotic ascites (controls). VEGF protein levels in ovarian, gastric, and colon cancer ascites were found to be increased 45, 23, and 12 times, respectively, compared with levels in cirrhotic ascites. Malignant ascites from patients with colon and gastric cancer caused an increase in permeability in HUVECs in all cases. Neutralizing VEGF activity in colon cancer ascites decreased in-vitro HUVEC permeability in three of four cases. Conclusions: VEGF protein levels are markedly elevated in malignant ascites. VEGF may play a role in malignant ascites formation by increasing endothelial cell permeability.

Original languageEnglish (US)
Pages (from-to)373-378
Number of pages6
JournalAnnals of Surgical Oncology
Volume6
Issue number4
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Fingerprint

Ascites
Vascular Endothelial Growth Factor A
Permeability
Human Umbilical Vein Endothelial Cells
Colonic Neoplasms
Stomach Neoplasms
Proteins
Endothelial Cells
Paracentesis
Propidium
Angiogenesis Inducing Agents
Capillary Permeability
Neutralizing Antibodies
Ovarian Neoplasms
Stomach
Colon
Enzyme-Linked Immunosorbent Assay

Keywords

  • Angiogenesis
  • Ascites
  • Colon cancer
  • Gastric cancer
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Markedly elevated levels of vascular endothelial growth factor in malignant ascites. / Zebrowski, Brian K.; Liu, Wenbiao; Ramirez, Karen; Akagi, Yoshito; Mills, Gordon; Ellis, Lee M.

In: Annals of Surgical Oncology, Vol. 6, No. 4, 01.01.1999, p. 373-378.

Research output: Contribution to journalArticle

Zebrowski, Brian K. ; Liu, Wenbiao ; Ramirez, Karen ; Akagi, Yoshito ; Mills, Gordon ; Ellis, Lee M. / Markedly elevated levels of vascular endothelial growth factor in malignant ascites. In: Annals of Surgical Oncology. 1999 ; Vol. 6, No. 4. pp. 373-378.
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AU - Ellis, Lee M.

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N2 - Background: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that also has the ability to increase vascular permeability. Malignant ascites has significant morbidity, but the mechanism of its development is unknown. Because of the permeability-inducing properties of VEGF, we hypothesized that malignant ascites formation is associated with high levels of VEGF. The purpose of our study was to determine the role of VEGF in malignant ascites formation. Methods: Ascites from 25 patients with gastric (n = 6), colon (n = 7), or ovarian (n = 12) cancers was collected by paracentesis or surgery. VEGF protein levels were determined by enzyme-linked immunosorbent assay. The effect of ascites on endothelial cell permeability was assessed by evaluating propidium iodide uptake by human umbilical vein endothelial cells (HUVECs) exposed to ascites. Neutralizing antibodies to VEGF added to ascites were used to determine the causal effect of VEGF in permeability induction. Results: VEGF protein levels were markedly increased in malignant ascites compared with levels in nonmalignant cirrhotic ascites (controls). VEGF protein levels in ovarian, gastric, and colon cancer ascites were found to be increased 45, 23, and 12 times, respectively, compared with levels in cirrhotic ascites. Malignant ascites from patients with colon and gastric cancer caused an increase in permeability in HUVECs in all cases. Neutralizing VEGF activity in colon cancer ascites decreased in-vitro HUVEC permeability in three of four cases. Conclusions: VEGF protein levels are markedly elevated in malignant ascites. VEGF may play a role in malignant ascites formation by increasing endothelial cell permeability.

AB - Background: Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that also has the ability to increase vascular permeability. Malignant ascites has significant morbidity, but the mechanism of its development is unknown. Because of the permeability-inducing properties of VEGF, we hypothesized that malignant ascites formation is associated with high levels of VEGF. The purpose of our study was to determine the role of VEGF in malignant ascites formation. Methods: Ascites from 25 patients with gastric (n = 6), colon (n = 7), or ovarian (n = 12) cancers was collected by paracentesis or surgery. VEGF protein levels were determined by enzyme-linked immunosorbent assay. The effect of ascites on endothelial cell permeability was assessed by evaluating propidium iodide uptake by human umbilical vein endothelial cells (HUVECs) exposed to ascites. Neutralizing antibodies to VEGF added to ascites were used to determine the causal effect of VEGF in permeability induction. Results: VEGF protein levels were markedly increased in malignant ascites compared with levels in nonmalignant cirrhotic ascites (controls). VEGF protein levels in ovarian, gastric, and colon cancer ascites were found to be increased 45, 23, and 12 times, respectively, compared with levels in cirrhotic ascites. Malignant ascites from patients with colon and gastric cancer caused an increase in permeability in HUVECs in all cases. Neutralizing VEGF activity in colon cancer ascites decreased in-vitro HUVEC permeability in three of four cases. Conclusions: VEGF protein levels are markedly elevated in malignant ascites. VEGF may play a role in malignant ascites formation by increasing endothelial cell permeability.

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