title: Transforming growth factor-beta signaling leads to uPA/PAI-1 activation and metastasis: a study on human breast cancer tissues.
abstract: 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.
authors.affiliation: Clinical and Experimental Pathology, Research Center Borstel, Parkallee 3a, 23845, Borstel, Germany, dlang@fz-borstel.de.
authors.forename: D S
authors.initials: DS
authors.lastname: Lang
authors.forename: S
authors.initials: S
authors.lastname: Marwitz
authors.forename: U
authors.initials: U
authors.lastname: Heilenkötter
authors.forename: W
authors.initials: W
authors.lastname: Schumm
authors.forename: O
authors.initials: O
authors.lastname: Behrens
authors.forename: R
authors.initials: R
authors.lastname: Simon
authors.forename: M
authors.initials: M
authors.lastname: Reck
authors.forename: E
authors.initials: E
authors.lastname: Vollmer
authors.forename: T
authors.initials: T
authors.lastname: Goldmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011379:Prognosis; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D016212:Transforming Growth Factor beta; D014568:Urokinase-Type Plasminogen Activator