title: Nerve growth factor and enhancement of proliferation, invasion, and tumorigenicity of pancreatic cancer cells.
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 beta-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.
authors.affiliation: Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Zhu
authors.forename: Jörg
authors.initials: J
authors.lastname: Kleeff
authors.forename: Hany
authors.initials: H
authors.lastname: Kayed
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Murray
authors.initials: M
authors.lastname: Korc
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Helmut
authors.initials: H
authors.lastname: Friess
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division; D003114:Colony-Forming Units Assay; D017931:DNA Primers / Q000737:chemistry; D018450:Disease Progression; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009368:Neoplasm Transplantation; D020932:Nerve Growth Factor / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000302:isolation & purification; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D020932:Nerve Growth Factor