Banca de DEFESA: RODRIGO PORPINO MAFRA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : RODRIGO PORPINO MAFRA
DATE: 14/02/2020
TIME: 14:00
LOCAL: DEPARTAMENTO DE ODONTOLOGIA
TITLE:

Plasminogen activator system in oral tongue squamous cell carcinoma: An immunohistochemical and in vitro study

KEY WORDS:

Oral tongue squamous cell carcinoma; Plasminogen activator system; Immunohistochemistry; Cell culture.

PAGES: 141
BIG AREA: Ciências da Saúde
AREA: Odontologia
SUMMARY:

Squamous cell carcinoma (SCC) is the most frequent malignant neoplasm of the oral cavity and has an unfavorable prognosis. Thus, studies have sought to clarify the role of biomarkers in the biological behavior of oral SCC. Within this context, urokinase-type plasminogen activator (uPA) and its receptor (uPAR), as well as plasminogen activator inhibitor 1 (PAI-1), are particularly interesting. The present study analyzed, by means of immunohistochemistry, the expressions of uPA, uPAR and PAI-1 in oral tongue SCC (OTSCC) and their relationship with clinicopathological parameters. This experiment also evaluated the in vitro effects of recombinant human PAI-1 (rhPAI-1) on the OTSCC-derived cell line SCC-25. The immunoexpression of uPA, uPAR and PAI-1 was analyzed semi-quantitatively in neoplastic cells of the invasion front of 60 OTSCC cases. Aiming to determine the association between immunohistochemical findings and clinicopathological variables, the cases were classified as low expression (≤50% of positive cells) and high expression (>50% of positive cells). The following groups were analyzed in the in vitro experiment: G0 (control; cells cultured in the absence of rhPAI-1), G10 (cells treated with 10 nM rhPAI-1), and G20 (cells treated with 20 nM rhPAI-1). Differences between these groups were investigated using the following assays: cell viability (Alamar Blue), cell cycle (staining with propidium iodide, PI), apoptosis/necrosis (staining with Annexin V and PI), migratory activity (Wound healing), and cell invasion (Transwell). Immunohistochemical analysis revealed high expression of uPA in most OTSCC  cases, but there were no significant associations with clinicopathological parameters (p>0.05). The high membrane expression of uPAR and PAI-1 was associated with local recurrence (p=0.019) and high tumor budding (p=0.046), respectively. Statistical analysis demonstrated the absence of significant associations between the immunohistochemical variables (uPA, uPAR and PAI-1) and prognostic indicators of OTSCC (disease-specific and disease-free survival) (p>0.05). In the in vitro experiment, 24 hours after administration of rhPAI-1, G10 and G20 exhibited greater cell viability compared to the control group (p=0.02), as well as increased progression to the S phase of the cell cycle (p=0.024). There were no significant differences in the percentages of apoptotic or necrotic cells between groups (p>0.05). In the groups cultured in the presence of rhPAI-1, migratory activity (p=0.039) and invasion potential (p=0.039) were found to be increased after 24 and 72 hours, respectively. The findings of this study suggest the involvement of uPA, uPAR and PAI-1 in the pathogenesis of OTSCC. Nevertheless, the expression of these biomarkers may not be related to the clinical outcome of patients. The in vitro results suggest that PAI-1 exerts stimulatory effects on cell proliferation, migration and invasion and may therefore contribute to the biological aggressiveness of OTSCC.

BANKING MEMBERS:
Interno - 2220417 - CARLOS AUGUSTO GALVAO BARBOZA
Externo à Instituição - CASSIANO FRANCISCO WEEGE NONAKA - UEPB
Externa à Instituição - CYNTIA HELENA PEREIRA DE CARVALHO - UFCG
Presidente - 344668 - LEAO PEREIRA PINTO
Interna - 346077 - LELIA BATISTA DE SOUZA