Abstract |
The epidermal growth factor receptor ( EGF-R) pathway plays a pivotal role in the progression of human gastric cancer. The angiogenic factor vascular endothelial growth factor ( VEGF) has been shown to be induced by EGF in various cancer cell lines. Neuropilin-1 (NRP-1) acts as a coreceptor for VEGF-165 and increases its affinity for VEGF receptor 2 (VEGFR-2) in endothelial cells. Furthermore, NRP-1 has been found to be expressed by tumour cells and has been shown to enhance tumour angiogenesis and growth in preclinical models. We examined the expression of NRP-1 mRNA and EGF-R protein in seven human gastric cancer cell lines. NRP-1 expression was expressed in five of seven cell lines, and EGF-R expression closely mirrored NRP-1 expression. Moreover, in EGF-R-positive NCI-N87 and ST-2 cells, EGF induced both NRP-1 and VEGF mRNA expression. C225, a monoclonal antibody to EGF-R, blocked EGF-induced NRP-1 and VEGF expression in NCI-N87 cells in a dose-dependent manner. The treatment of NCI-N87 cells with EGF resulted in increases in phosphorylation of Erk1/2, Akt, and P38. Blockade of the Erk, phosphatidylinositol-3 kinase/Akt, or P38 pathways in this cell line prevented EGF induction of NRP-1 and VEGF. These results suggest that regulation of NRP-1 expression in human gastric cancer is intimately associated with the EGF/ EGF-R system. Activation of EGF-R might contribute to gastric cancer angiogenesis by a mechanism that involves upregulation of VEGF and NRP-1 expression via multiple signalling pathways.
|
Authors | M Akagi, M Kawaguchi, W Liu, M F McCarty, A Takeda, F Fan, O Stoeltzing, A A Parikh, Y D Jung, C D Bucana, P F Mansfield, D J Hicklin, L M Ellis |
Journal | British journal of cancer
(Br J Cancer)
Vol. 88
Issue 5
Pg. 796-802
(Mar 10 2003)
ISSN: 0007-0920 [Print] England |
PMID | 12618892
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- DNA Primers
- Endothelial Growth Factors
- Intercellular Signaling Peptides and Proteins
- Lymphokines
- RNA, Messenger
- VEGFA protein, human
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
- Neuropilin-1
- Epidermal Growth Factor
|
Topics |
- Base Sequence
- Blotting, Northern
- Blotting, Western
- DNA Primers
- Endothelial Growth Factors
(genetics)
- Epidermal Growth Factor
(physiology)
- Gene Expression Regulation, Neoplastic
(physiology)
- Humans
- Immunohistochemistry
- Intercellular Signaling Peptides and Proteins
(genetics)
- Lymphokines
(genetics)
- Neuropilin-1
(genetics)
- Phosphorylation
- RNA, Messenger
(genetics)
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction
(physiology)
- Stomach Neoplasms
(metabolism, pathology)
- Tumor Cells, Cultured
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
|