Higher expression levels of TPA and C2erbB22 were observed in tumor tissue obtained from diagnostic biopsy and determined by immunohistochemistry, which indicated a higher risk of breast cancer in a total of 84 participants.
This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1).
Tissue-type plasminogen activator (tPA) has been shown to be associated with neoplastic transformation and the invasive phenotype for highly aggressive tumors; however, its role in breast cancer remains unclear.
This pattern of gene regulation suggested an inhibition of cell invasiveness because numerous clinical studies have indicated that low levels of urokinase plasminogen activator and high levels of tissue-type plasminogen activator in breast cancer are associated with favorable prognosis.