Vascular endothelial growth factor is an in vivo survival factor for tumor endothelium in a murine model of colorectal carcinoma liver metastases

Christiane J. Bruns, Wenbiao Liu, Darren W. Davis, Raymond M. Shaheen, David McConkey, Michael R. Wilson, Corazon D. Bucana, Daniel J. Hicklin, Lee M. Ellis

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Recent studies have suggested that vascular endothelial growth factor (VEGF), in addition to its proangiogenic properties, also functions as a survival factor for endothelial cells. The authors hypothesized that inhibition of VEGF activity by blockade of VEGF receptor-2 (R-2) function prevents angiogenesis and decreases tumor growth in colon carcinoma liver metastases. METHODS. Spleens of mice were injected with human colon carcinoma cells producing liver metastases. After 7 days of tumor growth, groups of mice received either antibody to VEGFR-2 (DC101) or phosphate-buffered saline (control). In a follow-up experiment, a similar treatment regimen was followed except that mice were sacrificed at 1-week intervals to assess the time course of endothelial cell and tumor cell apoptosis. RESULTS. After 21 days of therapy, the authors observed a significant decrease in vessel counts in liver metastases from human colon carcinoma in nude mice after therapy with VEGFR-2 antibody. Tumor cell apoptosis was increased significantly in the tumors of mice receiving DC101. Temporal studies with immunofluorescent double staining for the microvasculature and apoptotic cells revealed an increase in endothelial cell apoptosis that preceded an increase in tumor cell apoptosis. In vitro, treatment of human umbilical vein endothelial cells with antibody to VEGFR-2 produced a > 2.5-fold increase in endothelial cell apoptosis. CONCLUSIONS. Therapy targeting the VEGFR-2 inhibited tumor growth in a murine model of colon carcinoma liver metastasis. Surprisingly, this therapy did not only inhibit angiogenesis but also led to endothelial cell death. These findings suggest that VEGF, via VEGFR-2 signaling, functions as a survival factor for tumor endothelial cells in liver metastases from colon carcinoma. (C) 2000 American Cancer Society.

Original languageEnglish (US)
Pages (from-to)488-499
Number of pages12
JournalCancer
Volume89
Issue number3
DOIs
StatePublished - Aug 1 2000
Externally publishedYes

Fingerprint

Vascular Endothelial Growth Factor Receptor-2
Vascular Endothelial Growth Factor A
Endothelium
Colorectal Neoplasms
Neoplasm Metastasis
Survival
Endothelial Cells
Liver
Colon
Apoptosis
Neoplasms
Carcinoma
Antibodies
Growth
Time and Motion Studies
Human Umbilical Vein Endothelial Cells
Therapeutics
Microvessels
Nude Mice
Hepatocellular Carcinoma

Keywords

  • Angiogenesis
  • Antibodies
  • Apoptosis
  • Colon carcinoma
  • Endothelial cells
  • Immunohistochemistry
  • Metastasis
  • Receptor
  • Vascular endothelial growth factor
  • Vascular endothelial growth factor receptor-2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Vascular endothelial growth factor is an in vivo survival factor for tumor endothelium in a murine model of colorectal carcinoma liver metastases. / Bruns, Christiane J.; Liu, Wenbiao; Davis, Darren W.; Shaheen, Raymond M.; McConkey, David; Wilson, Michael R.; Bucana, Corazon D.; Hicklin, Daniel J.; Ellis, Lee M.

In: Cancer, Vol. 89, No. 3, 01.08.2000, p. 488-499.

Research output: Contribution to journalArticle

Bruns, Christiane J. ; Liu, Wenbiao ; Davis, Darren W. ; Shaheen, Raymond M. ; McConkey, David ; Wilson, Michael R. ; Bucana, Corazon D. ; Hicklin, Daniel J. ; Ellis, Lee M. / Vascular endothelial growth factor is an in vivo survival factor for tumor endothelium in a murine model of colorectal carcinoma liver metastases. In: Cancer. 2000 ; Vol. 89, No. 3. pp. 488-499.
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abstract = "BACKGROUND. Recent studies have suggested that vascular endothelial growth factor (VEGF), in addition to its proangiogenic properties, also functions as a survival factor for endothelial cells. The authors hypothesized that inhibition of VEGF activity by blockade of VEGF receptor-2 (R-2) function prevents angiogenesis and decreases tumor growth in colon carcinoma liver metastases. METHODS. Spleens of mice were injected with human colon carcinoma cells producing liver metastases. After 7 days of tumor growth, groups of mice received either antibody to VEGFR-2 (DC101) or phosphate-buffered saline (control). In a follow-up experiment, a similar treatment regimen was followed except that mice were sacrificed at 1-week intervals to assess the time course of endothelial cell and tumor cell apoptosis. RESULTS. After 21 days of therapy, the authors observed a significant decrease in vessel counts in liver metastases from human colon carcinoma in nude mice after therapy with VEGFR-2 antibody. Tumor cell apoptosis was increased significantly in the tumors of mice receiving DC101. Temporal studies with immunofluorescent double staining for the microvasculature and apoptotic cells revealed an increase in endothelial cell apoptosis that preceded an increase in tumor cell apoptosis. In vitro, treatment of human umbilical vein endothelial cells with antibody to VEGFR-2 produced a > 2.5-fold increase in endothelial cell apoptosis. CONCLUSIONS. Therapy targeting the VEGFR-2 inhibited tumor growth in a murine model of colon carcinoma liver metastasis. Surprisingly, this therapy did not only inhibit angiogenesis but also led to endothelial cell death. These findings suggest that VEGF, via VEGFR-2 signaling, functions as a survival factor for tumor endothelial cells in liver metastases from colon carcinoma. (C) 2000 American Cancer Society.",
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T1 - Vascular endothelial growth factor is an in vivo survival factor for tumor endothelium in a murine model of colorectal carcinoma liver metastases

AU - Bruns, Christiane J.

AU - Liu, Wenbiao

AU - Davis, Darren W.

AU - Shaheen, Raymond M.

AU - McConkey, David

AU - Wilson, Michael R.

AU - Bucana, Corazon D.

AU - Hicklin, Daniel J.

AU - Ellis, Lee M.

PY - 2000/8/1

Y1 - 2000/8/1

N2 - BACKGROUND. Recent studies have suggested that vascular endothelial growth factor (VEGF), in addition to its proangiogenic properties, also functions as a survival factor for endothelial cells. The authors hypothesized that inhibition of VEGF activity by blockade of VEGF receptor-2 (R-2) function prevents angiogenesis and decreases tumor growth in colon carcinoma liver metastases. METHODS. Spleens of mice were injected with human colon carcinoma cells producing liver metastases. After 7 days of tumor growth, groups of mice received either antibody to VEGFR-2 (DC101) or phosphate-buffered saline (control). In a follow-up experiment, a similar treatment regimen was followed except that mice were sacrificed at 1-week intervals to assess the time course of endothelial cell and tumor cell apoptosis. RESULTS. After 21 days of therapy, the authors observed a significant decrease in vessel counts in liver metastases from human colon carcinoma in nude mice after therapy with VEGFR-2 antibody. Tumor cell apoptosis was increased significantly in the tumors of mice receiving DC101. Temporal studies with immunofluorescent double staining for the microvasculature and apoptotic cells revealed an increase in endothelial cell apoptosis that preceded an increase in tumor cell apoptosis. In vitro, treatment of human umbilical vein endothelial cells with antibody to VEGFR-2 produced a > 2.5-fold increase in endothelial cell apoptosis. CONCLUSIONS. Therapy targeting the VEGFR-2 inhibited tumor growth in a murine model of colon carcinoma liver metastasis. Surprisingly, this therapy did not only inhibit angiogenesis but also led to endothelial cell death. These findings suggest that VEGF, via VEGFR-2 signaling, functions as a survival factor for tumor endothelial cells in liver metastases from colon carcinoma. (C) 2000 American Cancer Society.

AB - BACKGROUND. Recent studies have suggested that vascular endothelial growth factor (VEGF), in addition to its proangiogenic properties, also functions as a survival factor for endothelial cells. The authors hypothesized that inhibition of VEGF activity by blockade of VEGF receptor-2 (R-2) function prevents angiogenesis and decreases tumor growth in colon carcinoma liver metastases. METHODS. Spleens of mice were injected with human colon carcinoma cells producing liver metastases. After 7 days of tumor growth, groups of mice received either antibody to VEGFR-2 (DC101) or phosphate-buffered saline (control). In a follow-up experiment, a similar treatment regimen was followed except that mice were sacrificed at 1-week intervals to assess the time course of endothelial cell and tumor cell apoptosis. RESULTS. After 21 days of therapy, the authors observed a significant decrease in vessel counts in liver metastases from human colon carcinoma in nude mice after therapy with VEGFR-2 antibody. Tumor cell apoptosis was increased significantly in the tumors of mice receiving DC101. Temporal studies with immunofluorescent double staining for the microvasculature and apoptotic cells revealed an increase in endothelial cell apoptosis that preceded an increase in tumor cell apoptosis. In vitro, treatment of human umbilical vein endothelial cells with antibody to VEGFR-2 produced a > 2.5-fold increase in endothelial cell apoptosis. CONCLUSIONS. Therapy targeting the VEGFR-2 inhibited tumor growth in a murine model of colon carcinoma liver metastasis. Surprisingly, this therapy did not only inhibit angiogenesis but also led to endothelial cell death. These findings suggest that VEGF, via VEGFR-2 signaling, functions as a survival factor for tumor endothelial cells in liver metastases from colon carcinoma. (C) 2000 American Cancer Society.

KW - Angiogenesis

KW - Antibodies

KW - Apoptosis

KW - Colon carcinoma

KW - Endothelial cells

KW - Immunohistochemistry

KW - Metastasis

KW - Receptor

KW - Vascular endothelial growth factor

KW - Vascular endothelial growth factor receptor-2

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