Akt, COX-2, RUNX1 and MMPs expression in metastatic melanomas and biotechnology pr...
| Grant number: | 17/16102-8 |
| Support type: | Regular Research Grants |
| Duration: | September 01, 2017 - November 30, 2019 |
| Field of knowledge: | Health Sciences - Dentistry |
| Principal Investigator: | Jacks Jorge Junior |
| Grantee: | Jacks Jorge Junior |
| Home Institution: | Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil |
| Assoc. researchers: | Ciro Dantas Soares ; Edgard Graner |
Abstract
Melanoma is a neoplasm derived of melanocytes that is associated with aggressive clinical behavior and mainly by the high propensity for metastatic spread, which results in a poor prognosis. This tumor shows a heterogeneous clinical course. Patients with non-metastatic form of the disease (stage I and II) shows an overall survival rate of 97-53% in 5 years, however, in patients with metastatic melanoma (MM) this index ranges from 20-15% in the same period. Accumulating evidence in recent years about metastatic tumors focused great interest to determine molecular mechanisms underlying the ability of cancer cells to metastasize for development of new therapies with emphasis in patients with MM in advanced stage. Several molecules have been identified as having important roles to play in invasion and metastasis processes. Akt is associated with cell survival, metabolism regulation, migration and apoptosis. Recent studies reported that transcription factor RUNX1 activates the PI3K signaling pathway, resulting in phosphorylation of Akt, on the other hand, the cells showed inhibition of migration, apoptosis and invasion when Akt is silencing in vitro in many cells of different tumors. In cancer cells, Akt is also believed to be upregulated by the COX-2 pathway and is associated with a more aggressive phenotype in tumors, including by activation of metalloproteinases matrix, especially MMP-2 and MMP -9. Although the correlation of Akt and COX-2 has been related in several cancers and associated with metastases, their correlation in metastatic melanomas has not been widely reported. Thus, the project aims to study the relationship of signaling pathways (Akt, COX-2, RUNX1 and MMPs) in metastasis progression of melanoma model in vivo and in vitro. The slides will be scanned and analyzed using specific algorithms to quantify the expression intensity. Additionally, the biological role and effect of the Akt gene silencing in B16F10 cells will be investigated by in vitro assays: to determine the rate of cell death (necrosis and apoptosis), cell viability, proliferation, migration and invasion. Furthermore, B16F10 cells (silenced or not to Akt gene) will be injected in the tongue of C57BL/6 and chronological analysis of histological and biological events that occur during the metastatic process will be performed. (AU)