VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours

Y. Ohta, Vijayalakshmi Shridhar, R. K. Bright, G. P. Kalemkerian, W. Du, M. Carbone, Y. Watanabe, H. I. Pass

Research output: Contribution to journalArticle

278 Citations (Scopus)

Abstract

The vascular endothelial growth factor (VEGF) fmily is a novel regulator of endothelial cell proliferation. We assessed the mRNA expression of VEGF, VEGF type C (VEGF-C) and their receptors together with the microvessel density (VD) and microlymphatic vessel density (LVD) in pursuit of their connection and prognostic value in malignant pleural mesothelioma (MPM). We used four human MPM cell lines, 54 MPM tumours and five normal pleural tissues. Expression levels for receptors and ligands were assessed by semiquantitative reverse transcriptase polymerase chain reaction analysis. Microvessels were highlighted by immunohistochemical staining for factor VIII. The discrimination of lymphatics was performed by enzyme-histochemistry for 5'-nucleotidase after adequate inhibition of non-specific activity. The expression levels of VEGF, VEGF-C and VEGFRs were high in all MPM cell lines. The percentages of tumours with higher expression compared to the mean values of normal pleural tissues were 31.5% (17/54) for VEGF, 66.7% (36/54) for VEGF-C, 20.4% (11/54) for fms-like tyrosine kinase (flt)-1, 42.6% (23/54) for kinase insert domain-containing recepter (KDR) and 59.3% (32/54) for flt-4. Significant positive correlations were found between VEGF-C and flt-4, VEGF and KDR, VEGF and flt-1 in tumour tissues. The association between LVD and VEGF-C expression level was especially strong (P < 0.0001, r = 0.63). There were also significant correlations between LVD and flt-4, and VD and VEGF. No correlation, however, was found between LVD and nodal metastasis. VD was a negative prognostic indicator in this study. The associations between VEGF/VEGF-C and vessel density suggest that these factors play an important role in angiogenesis and lymphangiogenesis in this tumour, and assessment of vascularity may be a useful prognostic indicator for MPM patients.

Original languageEnglish (US)
Pages (from-to)54-61
Number of pages8
JournalBritish Journal of Cancer
Volume81
Issue number1
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Lymphangiogenesis
Vascular Endothelial Growth Factor C
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-1
Neoplasms
Microvessels
Phosphotransferases
Cell Line
5'-Nucleotidase
Malignant Mesothelioma
Factor VIII
Reverse Transcriptase Polymerase Chain Reaction
Reference Values
Endothelial Cells
Cell Proliferation
Staining and Labeling
Neoplasm Metastasis
Ligands
Messenger RNA

Keywords

  • Angiogenesis
  • Lymphangiogenesis
  • malignant mesothelioma
  • Vascular endothelial growth factor
  • VEGF
  • VEGF-C

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours. / Ohta, Y.; Shridhar, Vijayalakshmi; Bright, R. K.; Kalemkerian, G. P.; Du, W.; Carbone, M.; Watanabe, Y.; Pass, H. I.

In: British Journal of Cancer, Vol. 81, No. 1, 1999, p. 54-61.

Research output: Contribution to journalArticle

Ohta, Y. ; Shridhar, Vijayalakshmi ; Bright, R. K. ; Kalemkerian, G. P. ; Du, W. ; Carbone, M. ; Watanabe, Y. ; Pass, H. I. / VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours. In: British Journal of Cancer. 1999 ; Vol. 81, No. 1. pp. 54-61.
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AU - Shridhar, Vijayalakshmi

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AU - Du, W.

AU - Carbone, M.

AU - Watanabe, Y.

AU - Pass, H. I.

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