VEGF regulates PCB 104-mediated stimulation of permeability and transmigration of breast cancer cells in human microvascular endothelial cells

Sung Yong Eum, Yong Woo Lee, Bernhard Hennig, Michal J Toborek

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Polychlorinated biphenyl (PCB) congeners, a group of worldwide, persistent environmental contaminants, are known to cause carcinogenesis and tumor promotion, and may also affect the development of cancer metastasis. Because vascular endothelial cells create a selective barrier to the passage of cancer cells, we hypothesize that specific PCB congeners can disrupt endothelial integrity and increase the transendothelial migration of tumor cells. To examine this hypothesis, we elucidated the effects of 2,2′,4,6,6′- pentachlorobiphenyl (PCB 104), a representative of highly ortho-substituted non-coplanar PCB congeners, on the endothelial permeability and transendothelial migration of MDA-MB-231 breast cancer cells. Exposure of human microvascular endothelial cell 1 (HMEC-1) to PCB 104 induced endothelial hyperpermeability and markedly increased transendothelial migration of MDA-MB-231 cells. These effects were associated with overexpression of vascular endothelial growth factor (VEGF). PCB 104-mediated elevation of VEGF expression was induced by phosphatidylinositol 3-kinase (PI3K) but not affected by co-treatments with antioxidants or the NF-κB inhibitor SN50. In addition, the PI3K-dependent pathway was involved in PCB 104-induced activation of AP-1, a transcription factor implicated in the regulation of VEGF gene expression. The VEGF receptor (KDR/Flk-1) antagonist SU1498 and the PI3K inhibitor LY294002 inhibited PCB 104-induced hyperpermeability. These results indicate that PCB 104 may contribute to tumor metastasis by inducing VEGF overexpression that stimulates endothelial hyperpermeability and transendothelial migration of cancer cells.

Original languageEnglish
Pages (from-to)231-244
Number of pages14
JournalExperimental Cell Research
Volume296
Issue number2
DOIs
StatePublished - Jun 10 2004
Externally publishedYes

Fingerprint

Polychlorinated Biphenyls
Vascular Endothelial Growth Factor A
Permeability
Endothelial Cells
Breast Neoplasms
Transendothelial and Transepithelial Migration
Phosphatidylinositol 3-Kinase
Neoplasms
Neoplasm Metastasis
Vascular Endothelial Growth Factor Receptor
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Transcription Factor AP-1
Carcinogenesis
Antioxidants
Gene Expression

Keywords

  • bovine serum albumin
  • Breast cancer
  • BSA
  • EGCG
  • Endothelial cells
  • epigallocatechin-3-gallate
  • FBS
  • fetal bovine serum
  • Hank's balanced salt solution
  • HBSS
  • HMEC-1
  • human microvascular endothelial cell 1
  • Metastasis
  • PCB
  • PCB 104
  • Permeability
  • VEGF

ASJC Scopus subject areas

  • Cell Biology

Cite this

VEGF regulates PCB 104-mediated stimulation of permeability and transmigration of breast cancer cells in human microvascular endothelial cells. / Eum, Sung Yong; Lee, Yong Woo; Hennig, Bernhard; Toborek, Michal J.

In: Experimental Cell Research, Vol. 296, No. 2, 10.06.2004, p. 231-244.

Research output: Contribution to journalArticle

@article{1ab3a4d43ffa427a9285233234170449,
title = "VEGF regulates PCB 104-mediated stimulation of permeability and transmigration of breast cancer cells in human microvascular endothelial cells",
abstract = "Polychlorinated biphenyl (PCB) congeners, a group of worldwide, persistent environmental contaminants, are known to cause carcinogenesis and tumor promotion, and may also affect the development of cancer metastasis. Because vascular endothelial cells create a selective barrier to the passage of cancer cells, we hypothesize that specific PCB congeners can disrupt endothelial integrity and increase the transendothelial migration of tumor cells. To examine this hypothesis, we elucidated the effects of 2,2′,4,6,6′- pentachlorobiphenyl (PCB 104), a representative of highly ortho-substituted non-coplanar PCB congeners, on the endothelial permeability and transendothelial migration of MDA-MB-231 breast cancer cells. Exposure of human microvascular endothelial cell 1 (HMEC-1) to PCB 104 induced endothelial hyperpermeability and markedly increased transendothelial migration of MDA-MB-231 cells. These effects were associated with overexpression of vascular endothelial growth factor (VEGF). PCB 104-mediated elevation of VEGF expression was induced by phosphatidylinositol 3-kinase (PI3K) but not affected by co-treatments with antioxidants or the NF-κB inhibitor SN50. In addition, the PI3K-dependent pathway was involved in PCB 104-induced activation of AP-1, a transcription factor implicated in the regulation of VEGF gene expression. The VEGF receptor (KDR/Flk-1) antagonist SU1498 and the PI3K inhibitor LY294002 inhibited PCB 104-induced hyperpermeability. These results indicate that PCB 104 may contribute to tumor metastasis by inducing VEGF overexpression that stimulates endothelial hyperpermeability and transendothelial migration of cancer cells.",
keywords = "bovine serum albumin, Breast cancer, BSA, EGCG, Endothelial cells, epigallocatechin-3-gallate, FBS, fetal bovine serum, Hank's balanced salt solution, HBSS, HMEC-1, human microvascular endothelial cell 1, Metastasis, PCB, PCB 104, Permeability, VEGF",
author = "Eum, {Sung Yong} and Lee, {Yong Woo} and Bernhard Hennig and Toborek, {Michal J}",
year = "2004",
month = "6",
day = "10",
doi = "10.1016/j.yexcr.2004.01.030",
language = "English",
volume = "296",
pages = "231--244",
journal = "Experimental Cell Research",
issn = "0014-4827",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - VEGF regulates PCB 104-mediated stimulation of permeability and transmigration of breast cancer cells in human microvascular endothelial cells

AU - Eum, Sung Yong

AU - Lee, Yong Woo

AU - Hennig, Bernhard

AU - Toborek, Michal J

PY - 2004/6/10

Y1 - 2004/6/10

N2 - Polychlorinated biphenyl (PCB) congeners, a group of worldwide, persistent environmental contaminants, are known to cause carcinogenesis and tumor promotion, and may also affect the development of cancer metastasis. Because vascular endothelial cells create a selective barrier to the passage of cancer cells, we hypothesize that specific PCB congeners can disrupt endothelial integrity and increase the transendothelial migration of tumor cells. To examine this hypothesis, we elucidated the effects of 2,2′,4,6,6′- pentachlorobiphenyl (PCB 104), a representative of highly ortho-substituted non-coplanar PCB congeners, on the endothelial permeability and transendothelial migration of MDA-MB-231 breast cancer cells. Exposure of human microvascular endothelial cell 1 (HMEC-1) to PCB 104 induced endothelial hyperpermeability and markedly increased transendothelial migration of MDA-MB-231 cells. These effects were associated with overexpression of vascular endothelial growth factor (VEGF). PCB 104-mediated elevation of VEGF expression was induced by phosphatidylinositol 3-kinase (PI3K) but not affected by co-treatments with antioxidants or the NF-κB inhibitor SN50. In addition, the PI3K-dependent pathway was involved in PCB 104-induced activation of AP-1, a transcription factor implicated in the regulation of VEGF gene expression. The VEGF receptor (KDR/Flk-1) antagonist SU1498 and the PI3K inhibitor LY294002 inhibited PCB 104-induced hyperpermeability. These results indicate that PCB 104 may contribute to tumor metastasis by inducing VEGF overexpression that stimulates endothelial hyperpermeability and transendothelial migration of cancer cells.

AB - Polychlorinated biphenyl (PCB) congeners, a group of worldwide, persistent environmental contaminants, are known to cause carcinogenesis and tumor promotion, and may also affect the development of cancer metastasis. Because vascular endothelial cells create a selective barrier to the passage of cancer cells, we hypothesize that specific PCB congeners can disrupt endothelial integrity and increase the transendothelial migration of tumor cells. To examine this hypothesis, we elucidated the effects of 2,2′,4,6,6′- pentachlorobiphenyl (PCB 104), a representative of highly ortho-substituted non-coplanar PCB congeners, on the endothelial permeability and transendothelial migration of MDA-MB-231 breast cancer cells. Exposure of human microvascular endothelial cell 1 (HMEC-1) to PCB 104 induced endothelial hyperpermeability and markedly increased transendothelial migration of MDA-MB-231 cells. These effects were associated with overexpression of vascular endothelial growth factor (VEGF). PCB 104-mediated elevation of VEGF expression was induced by phosphatidylinositol 3-kinase (PI3K) but not affected by co-treatments with antioxidants or the NF-κB inhibitor SN50. In addition, the PI3K-dependent pathway was involved in PCB 104-induced activation of AP-1, a transcription factor implicated in the regulation of VEGF gene expression. The VEGF receptor (KDR/Flk-1) antagonist SU1498 and the PI3K inhibitor LY294002 inhibited PCB 104-induced hyperpermeability. These results indicate that PCB 104 may contribute to tumor metastasis by inducing VEGF overexpression that stimulates endothelial hyperpermeability and transendothelial migration of cancer cells.

KW - bovine serum albumin

KW - Breast cancer

KW - BSA

KW - EGCG

KW - Endothelial cells

KW - epigallocatechin-3-gallate

KW - FBS

KW - fetal bovine serum

KW - Hank's balanced salt solution

KW - HBSS

KW - HMEC-1

KW - human microvascular endothelial cell 1

KW - Metastasis

KW - PCB

KW - PCB 104

KW - Permeability

KW - VEGF

UR - http://www.scopus.com/inward/record.url?scp=2442570681&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2442570681&partnerID=8YFLogxK

U2 - 10.1016/j.yexcr.2004.01.030

DO - 10.1016/j.yexcr.2004.01.030

M3 - Article

C2 - 15149853

AN - SCOPUS:2442570681

VL - 296

SP - 231

EP - 244

JO - Experimental Cell Research

JF - Experimental Cell Research

SN - 0014-4827

IS - 2

ER -