ROLE OF ANTITUMOR IMMUNITY ON CHRONIC STRESS ENHANCEMENT OF SPONTANEOUS METASTASIS OF EL4 LYMPHOMA IN MICE. EFFECT OF FLUOXETINE AND SERTRALINE TREATMENT.

MARIA EMILIA DI ROSSO; MARÍA ROSA GONZALEZ MURANO; ANA MARÍA GENARO

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

SAIC, SAIB, SAI, SAA, SAB, SAB, SAFE, SAFIS, SAH, SAP

Many clinical studies have demonstrated that stress can promotethe dissemination of tumor cells. Moreover, antidepressants suchas fluoxetine (F) and sertraline (S) are able to modulate immunesystem and thus, tumor prognosis. We have previously reportedthat both F and S are able to prevent chronic stress enhancementof spontaneous metastasis in a murine model of lymphoma. In thiscontext, our aim was to study the effects of chronic stress and of antidepressanttreatment on tumor invasion taking into account the roleof anti-tumor immunity. For this purpose, female C57BL/6 mice weretreated with F or S and subjected (E) or not (C) to a heterotrophicchronic stress for five week and subcutaneously injected with EL4cells to generate a solid tumor. Specific cytotoxic activity against tumorcells was evaluated co-culturing spleen cells suspensions fromtumor bearing mice with labeled EL4 cells. The percentage of EL4cell lysis was significantly lower when incubated with splenocytes ofE mice compared to C mice (P<0.01). F and S treatment preventedthis effect. To further asses the involvement of immune system intumor invasion induced by chronic stress, irradiated animals weretransferred with lymphoid cells of C and E animals treated or notwith F and S and then inoculated with EL4 cells. The assessment ofspontaneous metastasis indicated that animals transferred with lymphoidcells of E animals have a higher incidence of liver metastasis(P=0.023) and a major number of liver metastatic nodules respect toanimals transferred with cell from C animals (P=0.027). In addition,tumor in animals transferred with cell from E mice that received For S administration have similar biological behavior than those of Canimals. Our results indicate the important role of immune system inthe stress induced stronger tumor invasion.