Nerve growth factor and enhancement of proliferation, invasion, and tumorigenicity of pancreatic cancer cells

Zhaowen Zhu, Jörg Kleeff, Hany Kayed, Li Wang, Murray Korc, Markus W. Büchler, Helmut Friess

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Nerve growth factor (NGF) exerts both stimulatory and inhibitory effects on neuronal and certain non-neuronal tumors. In pancreatic cancer NGF is overexpressed, and this overexpression is associated with increased perineural invasion. NGF has the potential to stimulate the growth of some pancreatic cancer cell lines, and this effect is mediated by the phosphorylation of tyrosine kinase receptor A and mitogen-activated protein kinase activation; it is dependent on the expression levels of tyrosine kinase receptor A and p75 receptors. To determine whether cancer cell-derived NGF can participate in the regulation of pancreatic cancer cell proliferation, PANC-1 human pancreatic cancer cells were stably transfected with a full-length human β-NGF expression vector. In vitro and in vivo growth characteristics were analyzed by proliferation assays and invasion assays and in a nude mouse tumor model. Stable transfection of NGF in PANC-1 cells resulted in enhanced anchorage-dependent growth, with a decrease in doubling times of up to 50%, and in an approximately twofold increase in anchorage-independent cell growth and cell invasion. Furthermore, stably transfected PANC-1 cells showed enhanced tumorigenicity in nude mice. These results suggest that NGF has the capacity to act in a paracrine and/or an autocrine manner in pancreatic cancer and that it enhances cancer cell growth and invasion in vivo, thereby contributing to the aggressiveness and poor prognosis of this disease.

Original languageEnglish (US)
Pages (from-to)138-147
Number of pages10
JournalMolecular Carcinogenesis
Volume35
Issue number3
DOIs
StatePublished - Nov 1 2002

Keywords

  • Cell invasion
  • Nerve growth factor
  • Pancreatic cancer
  • Tumorigenicity

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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    Zhu, Z., Kleeff, J., Kayed, H., Wang, L., Korc, M., Büchler, M. W., & Friess, H. (2002). Nerve growth factor and enhancement of proliferation, invasion, and tumorigenicity of pancreatic cancer cells. Molecular Carcinogenesis, 35(3), 138-147. https://doi.org/10.1002/mc.10083