Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma

Luigi Strizzi*, Alfonso Catalano, Giovina Vianale, Sara Orecchia, Angelo Casalini, Gianfranco Tassi, Riccardo Puntoni, Luciano Mutti, Antonio Procopio

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

290 Scopus citations

Abstract

Vascular endothelial growth factor (VEGF), a potent mitogen for vascular endothelium, is expressed in malignant pleural mesothelioma (MM). The present report examines the effect of VEGF on MM growth. Four MM cell lines produced significantly higher VEGF levels than normal mesothelial cells (1946 ± 14 pg/ml vs. 180 ± 17 pg/ml; p < 0.001). In addition, MM cells expressed the tyrosine kinase-related VEGF receptors Flt-1 and KDR. Recombinant human VEGF phosphorylated both Flt-1 and KDR and increased proliferation of all four MM cell lines in a dose-dependent fashion. Neutralizing antibodies against either VEGF, Flt-1 or KDR significantly reduced MM cellular proliferation. In addition, expression of VEGF, Flt-1, and KDR was observed in MM biopsies. Moreover, higher VECF levels were found in the pleural effusions of MM patients than in the effusions of patients with non-malignant pleural disease (1885.7 ± 894.9 pg/ml vs. 266.9 ± 180.5 pg/ml; p <0.001). Linear regression analysis showed a significant inverse correlation between serum VEGF levels and MM patient survival (r = 0.72; p <0.01). No correlation was found between tumour vessel density and either serum (r = 0.26; p = 0.42) or pleural effusion (r = 0.35; p = 0.26) VEGF levels. These results indicate that VEGF, via activation of its tyrosine kinase receptors, may be a key regulator of MM growth. In addition, VEGF production could have an impact on patient survival, not only by promoting tumour angiogenesis but also by directly stimulating tumour growth.

Original languageEnglish (US)
Pages (from-to)468-475
Number of pages8
JournalJournal of Pathology
Volume193
Issue number4
DOIs
StatePublished - Apr 17 2001

Keywords

  • Autocrine growth
  • Malignant pleural mesothelioma
  • VEGF

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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