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| Author(s): |
Ildefonso Alves da Silva Júnior
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2017-03-30 |
| Examining board members: |
Sonia Jancar Negro;
Luciana Nogueira de Sousa Andrade;
Alison Colquhoun;
Momtchilo Russo;
Jorge Sabbaga
|
| Advisor: | Sonia Jancar Negro; Ana Paula Lepique |
| Abstract | |
We investigate the role of the platelet activating factor receptor (PAFR) in tumors. We observed that PAFR KO animals are more resistant to the growth of B16F10 melanoma and TC-1 carcinoma than WT animals. PAFR KO had more infiltration of CD4+ cells, neutrophil and M1 macrophages than WT animals. Human carcinoma cells (C33 / SiHa / HeLa / SSC78 / SSC90) express PAFR and had their in vitro proliferation reduced by a PAFR antagonist and increased by the addition of PAF. Gamma irradiation induced PAFR ligands. Blocking PAFR during radiotherapy increased radiation-induced cell death. In tumor repopulation model, PAFR+ tumors (KBP) had an accelerated growth compared to PAFR- (KBM) tumors. Our data suggest that during irradiation occurs PAFR activation in tumor cells increasing their survival and proliferation. Also, irradiation promote activation of PAFR in macrophages by reprogramming them to a pro-tumor profile. We propose that PAFR represents a possible target for improving the efficacy of radiotherapy through inhibition of tumor repopulation. (AU) | |
| FAPESP's process: | 12/23538-3 - Role of PAF receptor in tumor cells and phenotype of macrophages |
| Grantee: | Ildefonso Alves da Silva Junior |
| Support Opportunities: | Scholarships in Brazil - Doctorate |