Thrombospondin-1 and transforming growth factor-beta1 promote breast tumor cell invasion through up-regulation of the plasminogen/plasmin system

Daniel Albo, David H. Berger, Thomas N. Wang, Xiaolong Hu, Vicki Rothman, George P. Tuszynski

Research output: Contribution to journalArticle

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Abstract

Background. Pericellular proteolysis is crucial in tumor cell invasion. The plasminogen/plasmin system is one of the main protease systems involved in cancer progression. Thrombospondin-1 (TSP-1), through activation of transforming growth factor-β1 (TGF-β1), up-regulates the main plasminogen activator, the urokinase-type plasminogen activator (uPA). The objectives of this study were to determine the role of TSP-1 and TGF-β1 in the localization of the plasminogen/plasmin system to the tumor cell surface by the uPA receptor (uPAR) and to determine its effect in breast tumor cell invasion. Methods. The effect of TSP-1 and TGF-β1 in uPAR expression was determined in MDA-MB-231 human breast cancer cells by enzyme-linked immunosorbent assay and Western blot analysis. Their effect and the role of the plasminogen/plasmin system in breast tumor cell invasion were studied with a Boyden Chamber assay. Results. uPAR expression was up-regulated more than twofold by both TSP-1 and TGF-β1. The effect of TSP-1 involved its receptor and the activation of TGF-β1 by TSP-1. Breast tumor cell invasion was up-regulated sevenfold to eightfold by both TSP-1 and TGF-β1 compared with the control group. Antibodies against uPA or uPAR neutralized the TSP- 1-and TGFβ1-promoted breast tumor cell invasion. Conclusions. TSP-1, through the activation of endogenous TGF-β1, up-regulates the plasminogen/plasmin system and promotes tumor cell invasion in breast cancer cells.

Original languageEnglish (US)
Pages (from-to)493-500
Number of pages8
JournalSurgery
Volume122
Issue number2
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

Fingerprint

Thrombospondin 1
Transforming Growth Factor beta1
Plasminogen
Fibrinolysin
Transforming Growth Factors
Up-Regulation
Breast Neoplasms
Urokinase-Type Plasminogen Activator
Neoplasms
Urokinase Plasminogen Activator Receptors
Plasminogen Activators
Proteolysis
Peptide Hydrolases
Western Blotting
Enzyme-Linked Immunosorbent Assay
Control Groups

ASJC Scopus subject areas

  • Surgery

Cite this

Thrombospondin-1 and transforming growth factor-beta1 promote breast tumor cell invasion through up-regulation of the plasminogen/plasmin system. / Albo, Daniel; Berger, David H.; Wang, Thomas N.; Hu, Xiaolong; Rothman, Vicki; Tuszynski, George P.

In: Surgery, Vol. 122, No. 2, 01.01.1997, p. 493-500.

Research output: Contribution to journalArticle

Albo, Daniel ; Berger, David H. ; Wang, Thomas N. ; Hu, Xiaolong ; Rothman, Vicki ; Tuszynski, George P. / Thrombospondin-1 and transforming growth factor-beta1 promote breast tumor cell invasion through up-regulation of the plasminogen/plasmin system. In: Surgery. 1997 ; Vol. 122, No. 2. pp. 493-500.
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abstract = "Background. Pericellular proteolysis is crucial in tumor cell invasion. The plasminogen/plasmin system is one of the main protease systems involved in cancer progression. Thrombospondin-1 (TSP-1), through activation of transforming growth factor-β1 (TGF-β1), up-regulates the main plasminogen activator, the urokinase-type plasminogen activator (uPA). The objectives of this study were to determine the role of TSP-1 and TGF-β1 in the localization of the plasminogen/plasmin system to the tumor cell surface by the uPA receptor (uPAR) and to determine its effect in breast tumor cell invasion. Methods. The effect of TSP-1 and TGF-β1 in uPAR expression was determined in MDA-MB-231 human breast cancer cells by enzyme-linked immunosorbent assay and Western blot analysis. Their effect and the role of the plasminogen/plasmin system in breast tumor cell invasion were studied with a Boyden Chamber assay. Results. uPAR expression was up-regulated more than twofold by both TSP-1 and TGF-β1. The effect of TSP-1 involved its receptor and the activation of TGF-β1 by TSP-1. Breast tumor cell invasion was up-regulated sevenfold to eightfold by both TSP-1 and TGF-β1 compared with the control group. Antibodies against uPA or uPAR neutralized the TSP- 1-and TGFβ1-promoted breast tumor cell invasion. Conclusions. TSP-1, through the activation of endogenous TGF-β1, up-regulates the plasminogen/plasmin system and promotes tumor cell invasion in breast cancer cells.",
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T1 - Thrombospondin-1 and transforming growth factor-beta1 promote breast tumor cell invasion through up-regulation of the plasminogen/plasmin system

AU - Albo, Daniel

AU - Berger, David H.

AU - Wang, Thomas N.

AU - Hu, Xiaolong

AU - Rothman, Vicki

AU - Tuszynski, George P.

PY - 1997/1/1

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N2 - Background. Pericellular proteolysis is crucial in tumor cell invasion. The plasminogen/plasmin system is one of the main protease systems involved in cancer progression. Thrombospondin-1 (TSP-1), through activation of transforming growth factor-β1 (TGF-β1), up-regulates the main plasminogen activator, the urokinase-type plasminogen activator (uPA). The objectives of this study were to determine the role of TSP-1 and TGF-β1 in the localization of the plasminogen/plasmin system to the tumor cell surface by the uPA receptor (uPAR) and to determine its effect in breast tumor cell invasion. Methods. The effect of TSP-1 and TGF-β1 in uPAR expression was determined in MDA-MB-231 human breast cancer cells by enzyme-linked immunosorbent assay and Western blot analysis. Their effect and the role of the plasminogen/plasmin system in breast tumor cell invasion were studied with a Boyden Chamber assay. Results. uPAR expression was up-regulated more than twofold by both TSP-1 and TGF-β1. The effect of TSP-1 involved its receptor and the activation of TGF-β1 by TSP-1. Breast tumor cell invasion was up-regulated sevenfold to eightfold by both TSP-1 and TGF-β1 compared with the control group. Antibodies against uPA or uPAR neutralized the TSP- 1-and TGFβ1-promoted breast tumor cell invasion. Conclusions. TSP-1, through the activation of endogenous TGF-β1, up-regulates the plasminogen/plasmin system and promotes tumor cell invasion in breast cancer cells.

AB - Background. Pericellular proteolysis is crucial in tumor cell invasion. The plasminogen/plasmin system is one of the main protease systems involved in cancer progression. Thrombospondin-1 (TSP-1), through activation of transforming growth factor-β1 (TGF-β1), up-regulates the main plasminogen activator, the urokinase-type plasminogen activator (uPA). The objectives of this study were to determine the role of TSP-1 and TGF-β1 in the localization of the plasminogen/plasmin system to the tumor cell surface by the uPA receptor (uPAR) and to determine its effect in breast tumor cell invasion. Methods. The effect of TSP-1 and TGF-β1 in uPAR expression was determined in MDA-MB-231 human breast cancer cells by enzyme-linked immunosorbent assay and Western blot analysis. Their effect and the role of the plasminogen/plasmin system in breast tumor cell invasion were studied with a Boyden Chamber assay. Results. uPAR expression was up-regulated more than twofold by both TSP-1 and TGF-β1. The effect of TSP-1 involved its receptor and the activation of TGF-β1 by TSP-1. Breast tumor cell invasion was up-regulated sevenfold to eightfold by both TSP-1 and TGF-β1 compared with the control group. Antibodies against uPA or uPAR neutralized the TSP- 1-and TGFβ1-promoted breast tumor cell invasion. Conclusions. TSP-1, through the activation of endogenous TGF-β1, up-regulates the plasminogen/plasmin system and promotes tumor cell invasion in breast cancer cells.

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