Altered expression of vascular endothelial growth factor, fibroblast growth factor-2 and endostatin in patients with hepatocellular carcinoma

Shuji Uematsu, Toshihiro Higashi, Kazuhiro Nouso, Kazuya Kariyama, Shin Ichiro Nakamura, Mayumi Suzuki, Harushige Nakatsukasa, Yoshiyuki Kobayashi, Tadashi Hanafusa, Takao Tsuji, Yasushi Shiratori

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Background: Advanced hepatocellular carcinoma (HCC) in humans is characterized by hypervascularity. In the present study, the expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2) and endostatin were analyzed in patients with chronic liver disease to clarify the effect of these major angiogenic factors. Methods: Serum concentrations of VEGF, FGF-2 and endostatin in 24 patients with HCC, 16 patients with liver cirrhosis (LC) and 13 healthy volunteers were measured by enzyme-linked immunosorbent assay. The expression of VEGF in 21 surgically resected HCC samples was analyzed by immunohistochemistry, and that of VEGF isoforms in 15 HCC samples was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Serum VEGF, FGF-2 and endostatin concentrations were significantly elevated in patients with HCC compared with healthy volunteers; but there was no significant difference between patients with HCC and those with non-HCC liver disease. Immunohistochemical analysis showed that VEGF protein was strongly expressed in both well-differentiated HCC cells and non-cancerous hepatocytes, whereas in moderately and poorly differentiated HCC the expression was stronger in the endothelial cells (EC) lining intratumor vessels than in the cancer cells. On RT-PCR for VEGF isoforms it was found that VEGF-121, VEGF-165 and VEGF-189 were expressed in all but one of the HCC samples and in all corresponding non-HCC samples. Conclusions: The results suggest that VEGF, FGF-2, and endostatin concentrations are elevated prior to the emergence of HCC and that the distribution of VEGF changes dynamically during the development of HCC.

Original languageEnglish
Pages (from-to)583-588
Number of pages6
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume20
Issue number4
DOIs
Publication statusPublished - 2005

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Endostatins
Fibroblast Growth Factor 2
Vascular Endothelial Growth Factor A
Hepatocellular Carcinoma
Reverse Transcriptase Polymerase Chain Reaction
Liver Diseases
Healthy Volunteers
Protein Isoforms
Carcinoma
Angiogenesis Inducing Agents
Serum
Liver Cirrhosis
Hepatocytes
Chronic Disease
Endothelial Cells

Keywords

  • Angiogenesis
  • Endostatin
  • Fibroblast growth factor-2
  • Hepatocellular carcinoma
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Altered expression of vascular endothelial growth factor, fibroblast growth factor-2 and endostatin in patients with hepatocellular carcinoma. / Uematsu, Shuji; Higashi, Toshihiro; Nouso, Kazuhiro; Kariyama, Kazuya; Nakamura, Shin Ichiro; Suzuki, Mayumi; Nakatsukasa, Harushige; Kobayashi, Yoshiyuki; Hanafusa, Tadashi; Tsuji, Takao; Shiratori, Yasushi.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 20, No. 4, 2005, p. 583-588.

Research output: Contribution to journalArticle

Uematsu, Shuji ; Higashi, Toshihiro ; Nouso, Kazuhiro ; Kariyama, Kazuya ; Nakamura, Shin Ichiro ; Suzuki, Mayumi ; Nakatsukasa, Harushige ; Kobayashi, Yoshiyuki ; Hanafusa, Tadashi ; Tsuji, Takao ; Shiratori, Yasushi. / Altered expression of vascular endothelial growth factor, fibroblast growth factor-2 and endostatin in patients with hepatocellular carcinoma. In: Journal of Gastroenterology and Hepatology (Australia). 2005 ; Vol. 20, No. 4. pp. 583-588.
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abstract = "Background: Advanced hepatocellular carcinoma (HCC) in humans is characterized by hypervascularity. In the present study, the expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2) and endostatin were analyzed in patients with chronic liver disease to clarify the effect of these major angiogenic factors. Methods: Serum concentrations of VEGF, FGF-2 and endostatin in 24 patients with HCC, 16 patients with liver cirrhosis (LC) and 13 healthy volunteers were measured by enzyme-linked immunosorbent assay. The expression of VEGF in 21 surgically resected HCC samples was analyzed by immunohistochemistry, and that of VEGF isoforms in 15 HCC samples was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Serum VEGF, FGF-2 and endostatin concentrations were significantly elevated in patients with HCC compared with healthy volunteers; but there was no significant difference between patients with HCC and those with non-HCC liver disease. Immunohistochemical analysis showed that VEGF protein was strongly expressed in both well-differentiated HCC cells and non-cancerous hepatocytes, whereas in moderately and poorly differentiated HCC the expression was stronger in the endothelial cells (EC) lining intratumor vessels than in the cancer cells. On RT-PCR for VEGF isoforms it was found that VEGF-121, VEGF-165 and VEGF-189 were expressed in all but one of the HCC samples and in all corresponding non-HCC samples. Conclusions: The results suggest that VEGF, FGF-2, and endostatin concentrations are elevated prior to the emergence of HCC and that the distribution of VEGF changes dynamically during the development of HCC.",
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T1 - Altered expression of vascular endothelial growth factor, fibroblast growth factor-2 and endostatin in patients with hepatocellular carcinoma

AU - Uematsu, Shuji

AU - Higashi, Toshihiro

AU - Nouso, Kazuhiro

AU - Kariyama, Kazuya

AU - Nakamura, Shin Ichiro

AU - Suzuki, Mayumi

AU - Nakatsukasa, Harushige

AU - Kobayashi, Yoshiyuki

AU - Hanafusa, Tadashi

AU - Tsuji, Takao

AU - Shiratori, Yasushi

PY - 2005

Y1 - 2005

N2 - Background: Advanced hepatocellular carcinoma (HCC) in humans is characterized by hypervascularity. In the present study, the expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2) and endostatin were analyzed in patients with chronic liver disease to clarify the effect of these major angiogenic factors. Methods: Serum concentrations of VEGF, FGF-2 and endostatin in 24 patients with HCC, 16 patients with liver cirrhosis (LC) and 13 healthy volunteers were measured by enzyme-linked immunosorbent assay. The expression of VEGF in 21 surgically resected HCC samples was analyzed by immunohistochemistry, and that of VEGF isoforms in 15 HCC samples was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Serum VEGF, FGF-2 and endostatin concentrations were significantly elevated in patients with HCC compared with healthy volunteers; but there was no significant difference between patients with HCC and those with non-HCC liver disease. Immunohistochemical analysis showed that VEGF protein was strongly expressed in both well-differentiated HCC cells and non-cancerous hepatocytes, whereas in moderately and poorly differentiated HCC the expression was stronger in the endothelial cells (EC) lining intratumor vessels than in the cancer cells. On RT-PCR for VEGF isoforms it was found that VEGF-121, VEGF-165 and VEGF-189 were expressed in all but one of the HCC samples and in all corresponding non-HCC samples. Conclusions: The results suggest that VEGF, FGF-2, and endostatin concentrations are elevated prior to the emergence of HCC and that the distribution of VEGF changes dynamically during the development of HCC.

AB - Background: Advanced hepatocellular carcinoma (HCC) in humans is characterized by hypervascularity. In the present study, the expressions of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2) and endostatin were analyzed in patients with chronic liver disease to clarify the effect of these major angiogenic factors. Methods: Serum concentrations of VEGF, FGF-2 and endostatin in 24 patients with HCC, 16 patients with liver cirrhosis (LC) and 13 healthy volunteers were measured by enzyme-linked immunosorbent assay. The expression of VEGF in 21 surgically resected HCC samples was analyzed by immunohistochemistry, and that of VEGF isoforms in 15 HCC samples was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Serum VEGF, FGF-2 and endostatin concentrations were significantly elevated in patients with HCC compared with healthy volunteers; but there was no significant difference between patients with HCC and those with non-HCC liver disease. Immunohistochemical analysis showed that VEGF protein was strongly expressed in both well-differentiated HCC cells and non-cancerous hepatocytes, whereas in moderately and poorly differentiated HCC the expression was stronger in the endothelial cells (EC) lining intratumor vessels than in the cancer cells. On RT-PCR for VEGF isoforms it was found that VEGF-121, VEGF-165 and VEGF-189 were expressed in all but one of the HCC samples and in all corresponding non-HCC samples. Conclusions: The results suggest that VEGF, FGF-2, and endostatin concentrations are elevated prior to the emergence of HCC and that the distribution of VEGF changes dynamically during the development of HCC.

KW - Angiogenesis

KW - Endostatin

KW - Fibroblast growth factor-2

KW - Hepatocellular carcinoma

KW - Vascular endothelial growth factor

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