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Expression and regulation of the novel vascular endothelial growth factor receptor neuropilin-1 by epidermal growth factor in human pancreatic carcinoma

  1. Alexander A. Parikh M.D.1,
  2. Wen Biao Liu M.D.2,
  3. Fan Fan M.S.2,
  4. Oliver Stoeltzing M.D.2,
  5. Niels Reinmuth M.D.2,
  6. Christiane J. Bruns M.D.2,
  7. Corazon D. Bucana Ph.D.2,
  8. Douglas B. Evans M.D.1,
  9. Lee M. Ellis M.D.1,2,†,*

Article first published online: 23 JUN 2003

DOI: 10.1002/cncr.11560

Issue

Cancer

Cancer

Volume 98, Issue 4, pages 720–729, 15 August 2003

Additional Information

How to Cite

Parikh, A. A., Liu, W. B., Fan, F., Stoeltzing, O., Reinmuth, N., Bruns, C. J., Bucana, C. D., Evans, D. B. and Ellis, L. M. (2003), Expression and regulation of the novel vascular endothelial growth factor receptor neuropilin-1 by epidermal growth factor in human pancreatic carcinoma. Cancer, 98: 720–729. doi: 10.1002/cncr.11560

Author Information

  1. 1

    Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

  2. 2

    Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

  1. †

    Fax: (713) 792-4689

*Department of Surgical Oncology, Box 444, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009

Publication History

  1. Issue published online: 1 AUG 2003
  2. Article first published online: 23 JUN 2003
  3. Manuscript Accepted: 5 MAY 2003
  4. Manuscript Revised: 18 MAR 2003
  5. Manuscript Received: 9 DEC 2002

Funded by

  • National Institutes of Health GRANT. Grant Number: T-32 09599
  • Lustgarten Foundation
  • Lockton Fund for Pancreatic Cancer Research

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Keywords:

  • angiogenesis;
  • pancreatic carcinoma;
  • neuropilin-1 (NRP-1);
  • epidermal growth factor (EGF);
  • vascular endothelial growth factor (VEGF)

Abstract

BACKGROUND

It was recently shown that neuropilin-1 (NRP-1), which was described originally as a receptor for the semaphorins/collapsins (ligands involved in neuronal guidance), is a coreceptor for vascular endothelial growth factor (VEGF) and increases the affinity of specific isoforms of VEGF to its receptor, VEGF-R2.

METHODS

The authors investigated the expression and regulation of NRP-1 in human pancreatic adenocarcinoma specimens and cell lines.

RESULTS

Immunohistochemical analysis revealed that NRP-1 was expressed in 12 of 12 human pancreatic adenocarcinoma specimens but was absent in nonmalignant pancreatic tissue. Northern blot analysis revealed NRP-1 mRNA expression in 8 of 11 human pancreatic adenocarcinoma cell lines. NRP-1 mRNA expression was increased by epidermal growth factor (EGF) but not by tumor necrosis factor α in several of the human pancreatic adenocarcinoma cell lines studied. Treating human Panc-48 adenocarcinoma cells with EGF activated Akt and Erk but not P-38. Blockade of the phosphatidylinositol-3 kinase (PI-3K)/Akt, mitogen-activated protein kinase (MAPK)/Erk, or P-38 pathways abrogated EGF-induced NRP-1 expression. Finally, EGF receptor blockade in vivo led to a decrease in NRP-1 expression in an orthotopic model of human pancreatic carcinoma.

CONCLUSIONS

NRP-1 is expressed in most human pancreatic adenocarcinomas and cell lines but not in nonmalignant pancreatic tissue. EGF regulates NRP-1 expression through the PI-3K/Akt and MAPK/Erk signaling pathways, and blockade of the EGF receptor is associated with decreased expression of NRP-1 in vivo. NRP-1 may act as a coreceptor for VEGF in pancreatic carcinoma, as it does in other tumor systems, thereby enhancing angiogenesis and the effect of VEGF on the growth of pancreatic adenocarcinoma. Cancer 2003;98:720–9. © 2003 American Cancer Society.

DOI 10.1002/cncr.11560

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