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PMID: 15161648 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Neuropilin-1 in human colon cancer: expression, regulation, and role in induction of angiogenesis.

The American journal of pathology ·Vol. 164 ·No. 6 ·2004-06-00 ·Pages 2139-51

Parikh AA, Fan F, Liu WB, Ahmad SA, Stoeltzing O, Reinmuth N, Bielenberg D, Bucana CD, Klagsbrun M, Ellis LM

Abstract

Neuropilin-1 (NRP-1), a recently identified co-receptor for vascular endothelial growth factor, is expressed by several nongastrointestinal tumor types and enhances prostate cancer angiogenesis and growth in preclinical models. We investigated the expression and regulation of NRP-1 and the effect of NRP-1 overexpression on angiogenesis and growth of human colon adenocarcinoma by immunohistochemistry and in situ hybridization. NRP-1 was expressed in 20 of 20 human colon adenocarcinoma specimens but not in the adjacent nonmalignant colonic mucosa. By reverse transcriptase-polymerase chain reaction analysis, NRP-1 mRNA was expressed in seven of seven colon adenocarcinoma cell lines. Subcutaneous xenografts of stably transfected KM12SM/LM2 human colon cancer cells overexpressing NRP-1 led to increased tumor growth and angiogenesis in nude mice. In in vitro assays, conditioned medium from NRP-1-transfected cell lines led to an increase in endothelial cell migration, but did not affect endothelial cell growth. Epidermal growth factor (EGF) led to induction of NRP-1 in human colon adenocarcinoma cells and selective blockade of the epidermal growth factor receptor (EGFR) decreased constitutive and EGF-induced NRP-1 expression. Blockade of the Erk 1/2 and P38 mitogen-activated protein kinase signaling pathways also led to a decrease in constitutive and EGF-induced NRP-1 expression. These findings demonstrate the ubiquitous expression of NRP-1 in human colon cancer and suggest that NRP-1 may contribute to colon cancer angiogenesis and growth. This study also suggests that EGF and mitogen-activated protein kinase signaling pathways play an important role in NRP-1 regulation in colon cancer cells.

MeSH Terms
Adenocarcinoma/blood supply,pathology Animals Cell Division Cell Line, Tumor Cloning, Molecular Colonic Neoplasms/blood supply,pathology DNA, Complementary/genetics Epidermal Growth Factor/pharmacology Gene Expression Regulation, Neoplastic/genetics Humans In Situ Hybridization Intestinal Mucosa/blood supply,pathology Mice Mice, Nude Mitogen-Activated Protein Kinases/metabolism Neovascularization, Pathologic/pathology Neuropilin-1/analysis,genetics,physiology Phosphorylation Recombinant Proteins/analysis Transfection Transplantation, Heterologous
Chemicals
DNA, Complementary Recombinant Proteins Neuropilin-1 Epidermal Growth Factor Mitogen-Activated Protein Kinases
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Parikh Alexander A
Departments of Surgical Oncology and Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA.
Fan Fan
Liu Wen Biao
Ahmad Syed A
Stoeltzing Oliver
Reinmuth Niels
Bielenberg Diane
Bucana Corazon D
Klagsbrun Michael
Ellis Lee M
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)63772-8
Published
2004-06-00
Pages
2139-51
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1615754
Subset
IM
Grants
NCI NIH HHS · CA-16672 · United States
NCI NIH HHS · P30 CA016672 · United States
PHS HHS · 37392 · United States
PHS HHS · 45448 · United States
NCI NIH HHS · CA-09599 · United States
NCI NIH HHS · T32 CA009599 · United States
External Links
PubMed source DOI: 10.1016/S0002-9440(10)63772-8 PMC Full Text View journal details
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