Loss of chemokine SDF-1α-mediated CXCR4 signalling and receptor internalization in human hepatoma cell line HepG2

Prasenjit Mitra, Asit De, Michael F. Ethier, Koshi Mimori, Karen Kodys, Kenji Shibuta, Masaki Mori, J. Mark Madison, Carol Miller-Graziano, Graham F. Barnard

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Expression of the chemokine stromal cell-derived factor-1α (SDF-1α) is absent from many carcinomas, including hepatomas. We note an early signalling defect in the hepatocellular carcinoma (HCC) cell line HepG2 that expresses the CXCR4 receptor and binds biotin-labelled SDF, but fails to stimulate downstream signalling events after engagement with SDF. In HepG2, the SDF/CXCR4 interaction did not result in calcium influx, phosphorylation and internalization of CXCR4, nor in a rapid phosphorylation of p44/42 MAP kinase. There were no CXCR4 mutations in the second chemokine binding loop or C terminal phosphorylation and internalization domains. The downstream signalling machinery in HepG2 appears to be intact since transfection of wild-type CXCR4 restored functional responsiveness. We conclude that HepG2 is unresponsive to SDF stimulation because of a defect located after receptor binding but before the activation of the signalling cascade. A hypothetical blocking molecule could hinder receptor internalization or CXCR4 signalling.

Original languageEnglish
Pages (from-to)311-319
Number of pages9
JournalCellular Signalling
Volume13
Issue number5
DOIs
Publication statusPublished - May 1 2001

Fingerprint

CXCR4 Receptors
Chemokine CXCL12
Chemokines
Hepatocellular Carcinoma
Phosphorylation
Cell Line
Biotin
Transfection
Phosphotransferases
Calcium
Carcinoma
Mutation

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Loss of chemokine SDF-1α-mediated CXCR4 signalling and receptor internalization in human hepatoma cell line HepG2. / Mitra, Prasenjit; De, Asit; Ethier, Michael F.; Mimori, Koshi; Kodys, Karen; Shibuta, Kenji; Mori, Masaki; Madison, J. Mark; Miller-Graziano, Carol; Barnard, Graham F.

In: Cellular Signalling, Vol. 13, No. 5, 01.05.2001, p. 311-319.

Research output: Contribution to journalArticle

Mitra, P, De, A, Ethier, MF, Mimori, K, Kodys, K, Shibuta, K, Mori, M, Madison, JM, Miller-Graziano, C & Barnard, GF 2001, 'Loss of chemokine SDF-1α-mediated CXCR4 signalling and receptor internalization in human hepatoma cell line HepG2', Cellular Signalling, vol. 13, no. 5, pp. 311-319. https://doi.org/10.1016/S0898-6568(01)00156-5
Mitra, Prasenjit ; De, Asit ; Ethier, Michael F. ; Mimori, Koshi ; Kodys, Karen ; Shibuta, Kenji ; Mori, Masaki ; Madison, J. Mark ; Miller-Graziano, Carol ; Barnard, Graham F. / Loss of chemokine SDF-1α-mediated CXCR4 signalling and receptor internalization in human hepatoma cell line HepG2. In: Cellular Signalling. 2001 ; Vol. 13, No. 5. pp. 311-319.
@article{b40b6a412b344de2be54c1c26bfff366,
title = "Loss of chemokine SDF-1α-mediated CXCR4 signalling and receptor internalization in human hepatoma cell line HepG2",
abstract = "Expression of the chemokine stromal cell-derived factor-1α (SDF-1α) is absent from many carcinomas, including hepatomas. We note an early signalling defect in the hepatocellular carcinoma (HCC) cell line HepG2 that expresses the CXCR4 receptor and binds biotin-labelled SDF, but fails to stimulate downstream signalling events after engagement with SDF. In HepG2, the SDF/CXCR4 interaction did not result in calcium influx, phosphorylation and internalization of CXCR4, nor in a rapid phosphorylation of p44/42 MAP kinase. There were no CXCR4 mutations in the second chemokine binding loop or C terminal phosphorylation and internalization domains. The downstream signalling machinery in HepG2 appears to be intact since transfection of wild-type CXCR4 restored functional responsiveness. We conclude that HepG2 is unresponsive to SDF stimulation because of a defect located after receptor binding but before the activation of the signalling cascade. A hypothetical blocking molecule could hinder receptor internalization or CXCR4 signalling.",
author = "Prasenjit Mitra and Asit De and Ethier, {Michael F.} and Koshi Mimori and Karen Kodys and Kenji Shibuta and Masaki Mori and Madison, {J. Mark} and Carol Miller-Graziano and Barnard, {Graham F.}",
year = "2001",
month = "5",
day = "1",
doi = "10.1016/S0898-6568(01)00156-5",
language = "English",
volume = "13",
pages = "311--319",
journal = "Cellular Signalling",
issn = "0898-6568",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Loss of chemokine SDF-1α-mediated CXCR4 signalling and receptor internalization in human hepatoma cell line HepG2

AU - Mitra, Prasenjit

AU - De, Asit

AU - Ethier, Michael F.

AU - Mimori, Koshi

AU - Kodys, Karen

AU - Shibuta, Kenji

AU - Mori, Masaki

AU - Madison, J. Mark

AU - Miller-Graziano, Carol

AU - Barnard, Graham F.

PY - 2001/5/1

Y1 - 2001/5/1

N2 - Expression of the chemokine stromal cell-derived factor-1α (SDF-1α) is absent from many carcinomas, including hepatomas. We note an early signalling defect in the hepatocellular carcinoma (HCC) cell line HepG2 that expresses the CXCR4 receptor and binds biotin-labelled SDF, but fails to stimulate downstream signalling events after engagement with SDF. In HepG2, the SDF/CXCR4 interaction did not result in calcium influx, phosphorylation and internalization of CXCR4, nor in a rapid phosphorylation of p44/42 MAP kinase. There were no CXCR4 mutations in the second chemokine binding loop or C terminal phosphorylation and internalization domains. The downstream signalling machinery in HepG2 appears to be intact since transfection of wild-type CXCR4 restored functional responsiveness. We conclude that HepG2 is unresponsive to SDF stimulation because of a defect located after receptor binding but before the activation of the signalling cascade. A hypothetical blocking molecule could hinder receptor internalization or CXCR4 signalling.

AB - Expression of the chemokine stromal cell-derived factor-1α (SDF-1α) is absent from many carcinomas, including hepatomas. We note an early signalling defect in the hepatocellular carcinoma (HCC) cell line HepG2 that expresses the CXCR4 receptor and binds biotin-labelled SDF, but fails to stimulate downstream signalling events after engagement with SDF. In HepG2, the SDF/CXCR4 interaction did not result in calcium influx, phosphorylation and internalization of CXCR4, nor in a rapid phosphorylation of p44/42 MAP kinase. There were no CXCR4 mutations in the second chemokine binding loop or C terminal phosphorylation and internalization domains. The downstream signalling machinery in HepG2 appears to be intact since transfection of wild-type CXCR4 restored functional responsiveness. We conclude that HepG2 is unresponsive to SDF stimulation because of a defect located after receptor binding but before the activation of the signalling cascade. A hypothetical blocking molecule could hinder receptor internalization or CXCR4 signalling.

UR - http://www.scopus.com/inward/record.url?scp=17344374988&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17344374988&partnerID=8YFLogxK

U2 - 10.1016/S0898-6568(01)00156-5

DO - 10.1016/S0898-6568(01)00156-5

M3 - Article

C2 - 11369512

AN - SCOPUS:17344374988

VL - 13

SP - 311

EP - 319

JO - Cellular Signalling

JF - Cellular Signalling

SN - 0898-6568

IS - 5

ER -