Differential involvement of TGF-β1 in mediating the motogenic effects of TSP-1 on endothelial cells, fibroblasts and oral tumour cells

K. Motegi, K. Harada, G. Ohe, Sarah J. Jones, Ian R. Ellis, Dorothy H. Crouch, Seth L. Schor, Ana M. Schor

Research output: Contribution to journalArticle

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Abstract

The role of TSP-1 in tumour growth and angiogenesis remains controversial, with both stimulatory and inhibitory roles proposed. The effects of TSP-1 on the migration of endothelial cells, fibroblast and oral tumour cell lines were examined using the transmembrane assay. TSP-1 induced a bi-phasic effect on human and bovine endothelial cells: stimulation at low concentrations (0.1-10 mu g/ml) and inhibition at high concentrations (25-100 mu g/ml). FGF-2-stimulated endothelial cell migration was either further stimulated or inhibited by TSP-1, following the same bi-phasic dose response as in the absence of FGF-2. In contrast, TSP-1 stimulated the migration of human fibroblast and oral tumour cells in a dose dependent manner; a plateau was reached with S-2S mu g/ml and no inhibitory effect was observed. These effects were partly neutralised by antibodies to alpha v beta 3 integrin. TGF-beta 1 (0.1-200ng/ml tested) mimicked the effects of TSP-1 on cell migration. Function-neutralising antibodies to TGF-1 completely abolished both the stimulatory and inhibitory effects of TSP-1 on endothelial migration, but had no effect on TSP-1-stimulated migration of fibroblast and oral tumour cells. The effects of TGF-beta 1 were not affected by antibodies to TSP-1. These results indicate that the effects of TSP-1 on endothelial cell migration are mediated by TGF-beta 1, whereas the effects on fibroblast and tumour cell migration are TGF-beta 1-independent. (c) 2008 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)2323-2333
Number of pages11
JournalExperimental Cell Research
Volume314
Issue number13
DOIs
Publication statusPublished - 1 Aug 2008

Keywords

  • TSP-1
  • TGF-beta 1
  • FGF-2
  • alpha v beta 3
  • migration
  • endothelial cells
  • oral tumour cells
  • fibroblasts
  • GROWTH-FACTOR-BETA
  • HUMAN SALIVARY-GLAND
  • ACTIVATOR INHIBITOR TYPE-1
  • TGF-BETA
  • IN-VITRO
  • UP-REGULATION
  • TRANSFORMING GROWTH-FACTOR-BETA-1
  • MESSENGER-RNA
  • CANCER-CELLS
  • INTEGRIN ALPHA(V)BETA(3)

Cite this

Motegi, K. ; Harada, K. ; Ohe, G. ; Jones, Sarah J. ; Ellis, Ian R. ; Crouch, Dorothy H. ; Schor, Seth L. ; Schor, Ana M. / Differential involvement of TGF-β1 in mediating the motogenic effects of TSP-1 on endothelial cells, fibroblasts and oral tumour cells. In: Experimental Cell Research. 2008 ; Vol. 314, No. 13. pp. 2323-2333.
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abstract = "The role of TSP-1 in tumour growth and angiogenesis remains controversial, with both stimulatory and inhibitory roles proposed. The effects of TSP-1 on the migration of endothelial cells, fibroblast and oral tumour cell lines were examined using the transmembrane assay. TSP-1 induced a bi-phasic effect on human and bovine endothelial cells: stimulation at low concentrations (0.1-10 mu g/ml) and inhibition at high concentrations (25-100 mu g/ml). FGF-2-stimulated endothelial cell migration was either further stimulated or inhibited by TSP-1, following the same bi-phasic dose response as in the absence of FGF-2. In contrast, TSP-1 stimulated the migration of human fibroblast and oral tumour cells in a dose dependent manner; a plateau was reached with S-2S mu g/ml and no inhibitory effect was observed. These effects were partly neutralised by antibodies to alpha v beta 3 integrin. TGF-beta 1 (0.1-200ng/ml tested) mimicked the effects of TSP-1 on cell migration. Function-neutralising antibodies to TGF-1 completely abolished both the stimulatory and inhibitory effects of TSP-1 on endothelial migration, but had no effect on TSP-1-stimulated migration of fibroblast and oral tumour cells. The effects of TGF-beta 1 were not affected by antibodies to TSP-1. These results indicate that the effects of TSP-1 on endothelial cell migration are mediated by TGF-beta 1, whereas the effects on fibroblast and tumour cell migration are TGF-beta 1-independent. (c) 2008 Elsevier Inc. All rights reserved.",
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Differential involvement of TGF-β1 in mediating the motogenic effects of TSP-1 on endothelial cells, fibroblasts and oral tumour cells. / Motegi, K.; Harada, K.; Ohe, G.; Jones, Sarah J.; Ellis, Ian R.; Crouch, Dorothy H.; Schor, Seth L.; Schor, Ana M.

In: Experimental Cell Research, Vol. 314, No. 13, 01.08.2008, p. 2323-2333.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Differential involvement of TGF-β1 in mediating the motogenic effects of TSP-1 on endothelial cells, fibroblasts and oral tumour cells

AU - Motegi, K.

AU - Harada, K.

AU - Ohe, G.

AU - Jones, Sarah J.

AU - Ellis, Ian R.

AU - Crouch, Dorothy H.

AU - Schor, Seth L.

AU - Schor, Ana M.

N1 - MEDLINE® is the source for the MeSH terms of this document.

PY - 2008/8/1

Y1 - 2008/8/1

N2 - The role of TSP-1 in tumour growth and angiogenesis remains controversial, with both stimulatory and inhibitory roles proposed. The effects of TSP-1 on the migration of endothelial cells, fibroblast and oral tumour cell lines were examined using the transmembrane assay. TSP-1 induced a bi-phasic effect on human and bovine endothelial cells: stimulation at low concentrations (0.1-10 mu g/ml) and inhibition at high concentrations (25-100 mu g/ml). FGF-2-stimulated endothelial cell migration was either further stimulated or inhibited by TSP-1, following the same bi-phasic dose response as in the absence of FGF-2. In contrast, TSP-1 stimulated the migration of human fibroblast and oral tumour cells in a dose dependent manner; a plateau was reached with S-2S mu g/ml and no inhibitory effect was observed. These effects were partly neutralised by antibodies to alpha v beta 3 integrin. TGF-beta 1 (0.1-200ng/ml tested) mimicked the effects of TSP-1 on cell migration. Function-neutralising antibodies to TGF-1 completely abolished both the stimulatory and inhibitory effects of TSP-1 on endothelial migration, but had no effect on TSP-1-stimulated migration of fibroblast and oral tumour cells. The effects of TGF-beta 1 were not affected by antibodies to TSP-1. These results indicate that the effects of TSP-1 on endothelial cell migration are mediated by TGF-beta 1, whereas the effects on fibroblast and tumour cell migration are TGF-beta 1-independent. (c) 2008 Elsevier Inc. All rights reserved.

AB - The role of TSP-1 in tumour growth and angiogenesis remains controversial, with both stimulatory and inhibitory roles proposed. The effects of TSP-1 on the migration of endothelial cells, fibroblast and oral tumour cell lines were examined using the transmembrane assay. TSP-1 induced a bi-phasic effect on human and bovine endothelial cells: stimulation at low concentrations (0.1-10 mu g/ml) and inhibition at high concentrations (25-100 mu g/ml). FGF-2-stimulated endothelial cell migration was either further stimulated or inhibited by TSP-1, following the same bi-phasic dose response as in the absence of FGF-2. In contrast, TSP-1 stimulated the migration of human fibroblast and oral tumour cells in a dose dependent manner; a plateau was reached with S-2S mu g/ml and no inhibitory effect was observed. These effects were partly neutralised by antibodies to alpha v beta 3 integrin. TGF-beta 1 (0.1-200ng/ml tested) mimicked the effects of TSP-1 on cell migration. Function-neutralising antibodies to TGF-1 completely abolished both the stimulatory and inhibitory effects of TSP-1 on endothelial migration, but had no effect on TSP-1-stimulated migration of fibroblast and oral tumour cells. The effects of TGF-beta 1 were not affected by antibodies to TSP-1. These results indicate that the effects of TSP-1 on endothelial cell migration are mediated by TGF-beta 1, whereas the effects on fibroblast and tumour cell migration are TGF-beta 1-independent. (c) 2008 Elsevier Inc. All rights reserved.

KW - TSP-1

KW - TGF-beta 1

KW - FGF-2

KW - alpha v beta 3

KW - migration

KW - endothelial cells

KW - oral tumour cells

KW - fibroblasts

KW - GROWTH-FACTOR-BETA

KW - HUMAN SALIVARY-GLAND

KW - ACTIVATOR INHIBITOR TYPE-1

KW - TGF-BETA

KW - IN-VITRO

KW - UP-REGULATION

KW - TRANSFORMING GROWTH-FACTOR-BETA-1

KW - MESSENGER-RNA

KW - CANCER-CELLS

KW - INTEGRIN ALPHA(V)BETA(3)

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U2 - 10.1016/j.yexcr.2008.04.013

DO - 10.1016/j.yexcr.2008.04.013

M3 - Article

VL - 314

SP - 2323

EP - 2333

JO - Experimental Cell Research

JF - Experimental Cell Research

SN - 0014-4827

IS - 13

ER -