Exp Clin Endocrinol Diabetes 2002; 110(8): 386-392
DOI: 10.1055/s-2002-36424
Article

© Johann Ambrosius Barth

In Vitro and in Vivo Angiogenesis in PC12 Pheochromocytoma Cells is Mediated by Vascular Endothelial Growth Factor

M. Middeke, S. Hoffmann, I. Hassan, A. Wunderlich, L. C. Hofbauer, A. Zielke
  • Departments of Surgery, and Internal Medicine (LCH), Philipps-University of Marburg, 35039 Marburg, Germany
Further Information

Publication History

received 14 March 2002 first decision 20 May 2002

accepted 28 June 2002

Publication Date:
08 January 2003 (online)

Summary

Angiogenesis, the formation of new blood vessels from existing vascular endothelium, is essential for tumor growth. Vascular endothelial growth factor (VEGF) is an endotheliumspecific mitogen and regulator of angiogenesis. Angiogenesis has been associated to the malignant phenotype of pheochromocytomas and is readily observed in experimental pheochromocytomas. Although VEGF gene expression has already been demonstrated in the rat PC12 cell line, the detailed mechanisms of action are not known. We have, therefore, studied angiogenesis in the rat PC12 pheochromocytoma cell line in vitro and in vivo. VEGF gene expression and accumulation of VEGF protein in cytoplasm and conditioned medium of PC12 cells was found. Conditioned medium from PC12 cells significantly increased proliferation of VEGF-dependent endothelial cells from human umbilical veins, and this effect reversed upon addition of a neutralizing anti-VEGF antibody. Dexamethasone and nerve growth factor (NGF) increased VEGF mRNA expression and accumulation of VEGF protein of PC12 subclones with established metastatic activity in vivo. PC12 cells xenotransplanted to nude mice had marked VEGF expression and induced host angiogenesis, confirmed by the presence of CD34-positive endothelial cells in the experimental PC12 tumors. When NGF-primed PC12 cells were immobilized in Matrigel supplemented with rising concentrations of the growth factor and xenotransplanted, increasing NGF resulted in tumors with smaller areas of necrosis and increased vital tumor volume.

These results suggest that VEGF is a mediator of angiogenesis in the PC12 pheochromocytoma cell line, and that dexamethasone and NGF affect VEGF expression. Our data further suggest that NGF may contribute to angiogenesis in experimental pheochromocytoma.

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M.D. Andreas Zielke

Department of Visceral, Thoracic and Vascular Surgery

Philipps-University of Marburg

Baldinger Straße

PoBox 100

35043 Marburg

Germany

Phone: + 49 6421 286 2572

Fax: + 49 6421 286 8995

Email: zielke@mailer.uni-marburg.de