Analysis of the role of plasminogen activator system proteins in oral tongue squamous cell carcinomas
Oral Squamous Cell Carcinoma; Urokinase-Type Plasminogen Activator; Immunohistochemistry; Cell Culture; Immunofluorescence.
Squamous cell carcinoma (SCC) is the most frequent malignant neoplasm of the oral cavity, and despite advances in treatments, prognosis remains poor. In this context, numerous researches have attempted to identify biomarkers related to the biological behavior of oral SCC, in order to enable more effective therapeutic strategies. Plasminogen activator system (SAP) comprises a set of molecules that act on several physiological and pathological phenomena, including angiogenesis, wound healing, invasion, and tumor metastasis. Its main components are urokinase-type plasminogen activator (uPA) and the receptor (uPAR), which interact and promote the conversion of plasminogen to plasmin. In turn, this enzyme can cause extracellular matrix remodeling, facilitating tumor invasion. The biological activity of uPA is regulated by inhibitory proteins, especially the inhibitor of plasminogen activator-1 (PAI-1). In view of the need to better understand the role of SAP in oral SCC, the objective of this research is to evaluate the immunoexpression of SAP proteins (uPA, uPAR, and PAI-1), and its correlations with the expression of invasion and cell proliferation markers (MMP-9 and Ki-67, respectively), and with clinicopathological parameters of oral tongue SCC (OTSCC). It is also intended to evaluate the in vitro effects of recombinant human PAI-1 protein (rhPAI-1) on SCC-25 cell line, derived from human OTSCC. By means of immunofluorescence technique, the expression of the uPA, uPAR and MMP-9 will be analyzed and compared between cells submitted and not submitted to treatment with rhPAI-1. In addition, the influence of rhPAI-1 on viability, proliferation, migration and cell invasion will be investigated by functional assays. This study aims to provide a better understanding of biological processes associated with aggressiveness of OTSCC.