Avaliação dos efeitos do anticorpo anti-fosfolipase A2 (IgY anti-BnSP-7) em diferentes etapas da progressão tumoral em células tumorais de próstata PC-3

Abstract

Prostate cancer (PCa) is among the main types of cancer between the male population, being a significant factor that leads this population to death, when late diagnosed. Due to the heterogeneity of this disease, the design of new treatments is essential. Phospholipases A2 (PLA2) are essential enzymes in the metabolism of phospholipids and are involved in several pathophysiologies, such as cancer. Recently, PLA2 has been recognized as possible biomarker, in view of its aberrant expression in several types of cancer, such as prostate cancer. This enzyme has a carcinogenic role due to the production of eicosanoids, which mediate pro-tumor effects, such as proliferation, resistance to apoptosis, transformation and metastasis. Furthermore, they are involved in inflammation, a pro-tumor event. Herein, we evaluated the cytotoxic potential of antiPLA2 polyclonal antibodies produced in chickens previously immunized with BnSP-7, a homologous phospholipase A2 isolated from the Bothrops pauloensis venom, against prostate tumor cells PC-3. The purification of these antibodies was successfully performed using affinity chromatography on a HiTrap IgY HP column. ELISA assays demonstrated the ability of the antibody to recognize its own antigen (BnSP-7), as well as isolated homologous PLA2 (BthTX-I and BthTX-II) and PLA2 present in the venom of B. pauloensis and B. jararacussu snakes. Cytotoxicity assays evaluated at 24 and 48h demonstrated that anti-BnSP-7 IgY has low cytotoxicity in PC-3 cells. Seeking to find out if this antibody could influence other stages in tumorigenesis, we evaluated the ability to inhibit adhesion and migration. Anti-BnSP-7 IgY was not able to inhibit PC-3 cell adhesion to extracellular matrix components, however, it inhibited cell migration. New assays are needed to elucidate the mechanism of action of this molecule. Taken together, these results suggest that PLA2 inhibition by antibodies is a potential biotechnological tool for anti-cancer therapies.