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Transforming Growth Factor-Beta Signaling Leads to uPA/PAI-1 Activation and Metastasis: A Study on Human Breast Cancer Tissues

2014; Springer Science+Business Media; Volume: 20; Issue: 3 Linguagem: Inglês

10.1007/s12253-014-9753-2

1532-2807

Dagmar S. Lang, Sebastian Marwitz, Uwe Heilenkötter, Walter R. Schumm, Otto K. Behrens, Ronald Simon, Martin Reck, E. Vollmer, Torsten Goldmann,

Clusterin in disease pathology

Metastasis represents a major problem in the treatment of patients with advanced primary breast cancer. Both Transforming Growth Factor-Beta (TGF-β) signaling and Plasminogen Activator (PA) components, urokinase-type Plasminogen Activator (uPA) and Plasminogen Activator Inhibitor-1 (PAI-1) represent a complex network crucial for such enhanced invasiveness of tumors and imply high prognostic/predictive and promising therapeutic potential. Therefore, protein expression of specific effector molecules comprising the main parts of the TGF-β signaling pathway were determined in HOPE-fixed human tumor tissues through IHC (Scoring) using tissue microarray (TMA) technique and correlated with respective uPA and PAI-1 levels determined earlier in the same TMAs through optimized IHC and semi-quantitative image analysis. TGF-β signaling was active in vast majority (96 %) of the tumor samples and 88 % of all cases were significantly correlated with established metastasis markers uPA and PAI-1. In addition, TGF-β was also closely associated with tumor size, nodal status and two steroid hormone receptors. Consistent interrelationships between TGF-β, PA components and additional tumor characteristics underline the superiority of such more comprising data with regards to confirming TGF-β signaling as a promising target system to inhibit metastasis in advanced breast cancer.