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Vascular endothelial growth factor is an autocrine growth factor in human malignant mesothelioma
Author(s) -
Strizzi Luigi,
Catalano Alfonso,
Vianale Giovina,
Orecchia Sara,
Casalini Angelo,
Tassi Gianfranco,
Puntoni Riccardo,
Mutti Luciano,
Procopio Antonio
Publication year - 2001
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.824
Subject(s) - autocrine signalling , mesothelioma , vascular endothelial growth factor , vascular endothelial growth factor c , factor (programming language) , growth factor , cancer research , medicine , vegf receptors , pathology , vascular endothelial growth factor a , oncology , computer science , receptor , programming language
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 VEGF 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. Copyright © 2001 John Wiley & Sons, Ltd.