Vascular endothelial growth factor drives autocrine epithelial cell proliferation and survival in chronic rhinosinusitis with nasal polyposis

Hyun Sil Lee, Allen Myers, Jean Kim

Research output: Contribution to journalArticle

Abstract

Rationale: The pathogenesis of nasal polyps in chronic rhinosinusitis is poorly understood. Objectives: These studies seek to implicate a functional role for vascular endothelial growth factor (VEGF) in perpetuating primary nasal epithelial cell overgrowth, a key feature of hyperplastic polyps. Methods: Comparison of VEGF and receptor expression was assessed by ELISA of nasal lavage, immunohistochemistry of sinus tissue, flow cytometry of nasal epithelial cells, and ELISA of supernatants. VEGFdependent cell growth and apoptosis were assessed with blocking antibodies to VEGF, their receptors, or small interfering RNA knockdown of neuropilin-1 by cell proliferation assays and flow cytometric binding of annexin V. Measurements and Main Results: VEGF protein was sevenfold higher in nasal lavage from patients with polyposis compared with control subjects (P,0.001).Wealso report elevated expression ofVEGF(P, 0.012), receptors VEGFR2 and phospho-VEGFR2 (both P,0.04), and identification of VEGF coreceptor neuropilin-1 in these tissues. Nasal epithelial cells from patients with polyps demonstrated faster growth rates (P , 0.005). Exposure of cells to blocking antibodies against VEGF resulted in inhibition of cell growth (P , 0.05). VEGF receptor blockade required blockade of neuropilin-1 (P , 0.05) and resulted in increased apoptosis (P , 0.001) and inhibition of autocrine epithelial VEGF production (P , 0.05). Conclusions: These data demonstrate that VEGF is a novel biomarker for chronic rhinosinusitis with hyperplastic sinonasal polyposis that functions in an autocrine feed-forward manner to promote nasal epithelial cell growth and to inhibit apoptosis. These findings implicate a previously unrecognized and novel role of VEGF functioning through neuropilin-1 on nonneoplastic primary human airway epithelial cells, to amplify cell growth, contributing to exuberant hyperplastic polyposis.

Original languageEnglish (US)
Pages (from-to)1056-1067
Number of pages12
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume180
Issue number11
DOIs
StatePublished - Dec 1 2009

Fingerprint

Nose
Vascular Endothelial Growth Factor A
Neuropilin-1
Cell Survival
Epithelial Cells
Cell Proliferation
Vascular Endothelial Growth Factor Receptor
Nasal Lavage
Growth
Blocking Antibodies
Apoptosis
Polyps
Enzyme-Linked Immunosorbent Assay
Nasal Polyps
Annexin A5
Small Interfering RNA
Flow Cytometry
Biomarkers
Immunohistochemistry
Proteins

Keywords

  • Apoptosis
  • Chronic rhinosinusitis with nasal polyposis
  • Epithelial cell growth
  • Neuropilin-1
  • Vascular endothelial cell growth factor

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

@article{a0603a2f09fb4ddf8015d1d596cff498,
title = "Vascular endothelial growth factor drives autocrine epithelial cell proliferation and survival in chronic rhinosinusitis with nasal polyposis",
abstract = "Rationale: The pathogenesis of nasal polyps in chronic rhinosinusitis is poorly understood. Objectives: These studies seek to implicate a functional role for vascular endothelial growth factor (VEGF) in perpetuating primary nasal epithelial cell overgrowth, a key feature of hyperplastic polyps. Methods: Comparison of VEGF and receptor expression was assessed by ELISA of nasal lavage, immunohistochemistry of sinus tissue, flow cytometry of nasal epithelial cells, and ELISA of supernatants. VEGFdependent cell growth and apoptosis were assessed with blocking antibodies to VEGF, their receptors, or small interfering RNA knockdown of neuropilin-1 by cell proliferation assays and flow cytometric binding of annexin V. Measurements and Main Results: VEGF protein was sevenfold higher in nasal lavage from patients with polyposis compared with control subjects (P,0.001).Wealso report elevated expression ofVEGF(P, 0.012), receptors VEGFR2 and phospho-VEGFR2 (both P,0.04), and identification of VEGF coreceptor neuropilin-1 in these tissues. Nasal epithelial cells from patients with polyps demonstrated faster growth rates (P , 0.005). Exposure of cells to blocking antibodies against VEGF resulted in inhibition of cell growth (P , 0.05). VEGF receptor blockade required blockade of neuropilin-1 (P , 0.05) and resulted in increased apoptosis (P , 0.001) and inhibition of autocrine epithelial VEGF production (P , 0.05). Conclusions: These data demonstrate that VEGF is a novel biomarker for chronic rhinosinusitis with hyperplastic sinonasal polyposis that functions in an autocrine feed-forward manner to promote nasal epithelial cell growth and to inhibit apoptosis. These findings implicate a previously unrecognized and novel role of VEGF functioning through neuropilin-1 on nonneoplastic primary human airway epithelial cells, to amplify cell growth, contributing to exuberant hyperplastic polyposis.",
keywords = "Apoptosis, Chronic rhinosinusitis with nasal polyposis, Epithelial cell growth, Neuropilin-1, Vascular endothelial cell growth factor",
author = "Lee, {Hyun Sil} and Allen Myers and Jean Kim",
year = "2009",
month = "12",
day = "1",
doi = "10.1164/rccm.200905-0740OC",
language = "English (US)",
volume = "180",
pages = "1056--1067",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "11",

}

TY - JOUR

T1 - Vascular endothelial growth factor drives autocrine epithelial cell proliferation and survival in chronic rhinosinusitis with nasal polyposis

AU - Lee, Hyun Sil

AU - Myers, Allen

AU - Kim, Jean

PY - 2009/12/1

Y1 - 2009/12/1

N2 - Rationale: The pathogenesis of nasal polyps in chronic rhinosinusitis is poorly understood. Objectives: These studies seek to implicate a functional role for vascular endothelial growth factor (VEGF) in perpetuating primary nasal epithelial cell overgrowth, a key feature of hyperplastic polyps. Methods: Comparison of VEGF and receptor expression was assessed by ELISA of nasal lavage, immunohistochemistry of sinus tissue, flow cytometry of nasal epithelial cells, and ELISA of supernatants. VEGFdependent cell growth and apoptosis were assessed with blocking antibodies to VEGF, their receptors, or small interfering RNA knockdown of neuropilin-1 by cell proliferation assays and flow cytometric binding of annexin V. Measurements and Main Results: VEGF protein was sevenfold higher in nasal lavage from patients with polyposis compared with control subjects (P,0.001).Wealso report elevated expression ofVEGF(P, 0.012), receptors VEGFR2 and phospho-VEGFR2 (both P,0.04), and identification of VEGF coreceptor neuropilin-1 in these tissues. Nasal epithelial cells from patients with polyps demonstrated faster growth rates (P , 0.005). Exposure of cells to blocking antibodies against VEGF resulted in inhibition of cell growth (P , 0.05). VEGF receptor blockade required blockade of neuropilin-1 (P , 0.05) and resulted in increased apoptosis (P , 0.001) and inhibition of autocrine epithelial VEGF production (P , 0.05). Conclusions: These data demonstrate that VEGF is a novel biomarker for chronic rhinosinusitis with hyperplastic sinonasal polyposis that functions in an autocrine feed-forward manner to promote nasal epithelial cell growth and to inhibit apoptosis. These findings implicate a previously unrecognized and novel role of VEGF functioning through neuropilin-1 on nonneoplastic primary human airway epithelial cells, to amplify cell growth, contributing to exuberant hyperplastic polyposis.

AB - Rationale: The pathogenesis of nasal polyps in chronic rhinosinusitis is poorly understood. Objectives: These studies seek to implicate a functional role for vascular endothelial growth factor (VEGF) in perpetuating primary nasal epithelial cell overgrowth, a key feature of hyperplastic polyps. Methods: Comparison of VEGF and receptor expression was assessed by ELISA of nasal lavage, immunohistochemistry of sinus tissue, flow cytometry of nasal epithelial cells, and ELISA of supernatants. VEGFdependent cell growth and apoptosis were assessed with blocking antibodies to VEGF, their receptors, or small interfering RNA knockdown of neuropilin-1 by cell proliferation assays and flow cytometric binding of annexin V. Measurements and Main Results: VEGF protein was sevenfold higher in nasal lavage from patients with polyposis compared with control subjects (P,0.001).Wealso report elevated expression ofVEGF(P, 0.012), receptors VEGFR2 and phospho-VEGFR2 (both P,0.04), and identification of VEGF coreceptor neuropilin-1 in these tissues. Nasal epithelial cells from patients with polyps demonstrated faster growth rates (P , 0.005). Exposure of cells to blocking antibodies against VEGF resulted in inhibition of cell growth (P , 0.05). VEGF receptor blockade required blockade of neuropilin-1 (P , 0.05) and resulted in increased apoptosis (P , 0.001) and inhibition of autocrine epithelial VEGF production (P , 0.05). Conclusions: These data demonstrate that VEGF is a novel biomarker for chronic rhinosinusitis with hyperplastic sinonasal polyposis that functions in an autocrine feed-forward manner to promote nasal epithelial cell growth and to inhibit apoptosis. These findings implicate a previously unrecognized and novel role of VEGF functioning through neuropilin-1 on nonneoplastic primary human airway epithelial cells, to amplify cell growth, contributing to exuberant hyperplastic polyposis.

KW - Apoptosis

KW - Chronic rhinosinusitis with nasal polyposis

KW - Epithelial cell growth

KW - Neuropilin-1

KW - Vascular endothelial cell growth factor

UR - http://www.scopus.com/inward/record.url?scp=72749119015&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=72749119015&partnerID=8YFLogxK

U2 - 10.1164/rccm.200905-0740OC

DO - 10.1164/rccm.200905-0740OC

M3 - Article

C2 - 19762561

AN - SCOPUS:72749119015

VL - 180

SP - 1056

EP - 1067

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 11

ER -