Transforming growth factor-β1 enhances the invasiveness of human MDA- MB-231 breast cancer cells by up-regulating urokinase activity

Antonietta R. Farina, Anna Coppa, Antonella Tiberio, Antonella Tacconelli, Alessandra Turco, Gulia Colletta, Alberto Gulino, Andrew R. Mackay

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Transforming growth factor-beta (TGFβ1) enhances human MDA-MB-231 breast tumour cell invasion of reconstituted basement membrane in vitro but does not inhibit proliferation of this cell line. In contrast to basal invasion, which is plasmin-, urokinase (uPA)-, tissue-type plasminogen activator (t-PA)-, matrix metalloproteinase (MMP)-9- and TIMP-1-inhibitable MMP-dependent, TGFβ1 enhanced-invasion is dependent upon plasmin and uPA activity but does not appear to involve t-PA-, MMP9- or TIMP-1-inhibitable MMPs, as judged by inhibitor studies. Enhanced invasion is associated with increased u-PA, UPAR, PAI-1, MT-MMP-1, MMP-9 and TIMP-1 expression; with reduced t-PA, MMP-1 and MMP-3 expression; and with the induction of membrane MMP-9 association. The net result of these changes includes increased secreted, but not membrane-associated, uPA levels and activity and reduced secreted levels of plasmin and APMA-activatable gelatinolytic, collagenolytic and caseinolytic MMP activity but no change in membrane-associated gelatinolytic activity, despite increased MT-MMP-1 expression and MMP-9 membrane association. TGFβ1 does not induce MMP-2 expression. Our data indicate that TGFβ1 can promote the malignant behaviour of MDA-MB-231 cells refractory to TGFβ1-mediated proliferation control by enhancing their invasive capacity. We suggest that this results from the action of a uPA/plasmin-dependent mechanism resulting from stimulation of uPA expression, secretion and subsequent activity, despite elevated PAI-1 inhibitor levels.

Original languageEnglish
Pages (from-to)721-730
Number of pages10
JournalInternational Journal of Cancer
Volume75
Issue number5
DOIs
Publication statusPublished - Mar 2 1998

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Fibrinolysin
Matrix Metalloproteinase 9
Urokinase-Type Plasminogen Activator
Transforming Growth Factors
Matrix Metalloproteinase 1
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinases
Breast Neoplasms
Membranes
Plasminogen Activators
Plasminogen Activator Inhibitor 1
Matrix Metalloproteinase 3
Matrix Metalloproteinase 2
Tissue Plasminogen Activator
Basement Membrane
Transforming Growth Factor beta
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Transforming growth factor-β1 enhances the invasiveness of human MDA- MB-231 breast cancer cells by up-regulating urokinase activity. / Farina, Antonietta R.; Coppa, Anna; Tiberio, Antonella; Tacconelli, Antonella; Turco, Alessandra; Colletta, Gulia; Gulino, Alberto; Mackay, Andrew R.

In: International Journal of Cancer, Vol. 75, No. 5, 02.03.1998, p. 721-730.

Research output: Contribution to journalArticle

Farina, Antonietta R. ; Coppa, Anna ; Tiberio, Antonella ; Tacconelli, Antonella ; Turco, Alessandra ; Colletta, Gulia ; Gulino, Alberto ; Mackay, Andrew R. / Transforming growth factor-β1 enhances the invasiveness of human MDA- MB-231 breast cancer cells by up-regulating urokinase activity. In: International Journal of Cancer. 1998 ; Vol. 75, No. 5. pp. 721-730.
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AU - Tacconelli, Antonella

AU - Turco, Alessandra

AU - Colletta, Gulia

AU - Gulino, Alberto

AU - Mackay, Andrew R.

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