Beneficial effect of fluoxetine and dertraline on chronic stress-induced tumor crowth and cell dissemination in a mouse model of lymphoma : crucial role of antitumor immunity

Abstract: Clinical data and experimental studies have suggested a relationship between psychosocial factors and cancer prognosis. Both, stress effects on the immune system and on tumor biology were analyzed independently. However, there are few studies regarding the stress influence on the interplay...

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Autores principales: Di Rosso, María Emilia, Sterle, Helena Andrea, Cremaschi, Graciela A., Genaro, Ana María
Formato: Artículo
Lenguaje:Inglés
Publicado: Frontiers 2019
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Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8672
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id I33-R139123456789-8672
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic TUMORES
SISTEMA LINFATICO
CANCER
SEROTONINA
ANTIDEPRESIVOS
ESTRES
SISTEMA INMUNOLOGICO
spellingShingle TUMORES
SISTEMA LINFATICO
CANCER
SEROTONINA
ANTIDEPRESIVOS
ESTRES
SISTEMA INMUNOLOGICO
Di Rosso, María Emilia
Sterle, Helena Andrea
Cremaschi, Graciela A.
Genaro, Ana María
Beneficial effect of fluoxetine and dertraline on chronic stress-induced tumor crowth and cell dissemination in a mouse model of lymphoma : crucial role of antitumor immunity
topic_facet TUMORES
SISTEMA LINFATICO
CANCER
SEROTONINA
ANTIDEPRESIVOS
ESTRES
SISTEMA INMUNOLOGICO
description Abstract: Clinical data and experimental studies have suggested a relationship between psychosocial factors and cancer prognosis. Both, stress effects on the immune system and on tumor biology were analyzed independently. However, there are few studies regarding the stress influence on the interplay between the immune system and tumor biology. Moreover, antidepressants have been used in patients with cancer to alleviate mood disorders. Nevertheless, there is contradictory evidence about their action on cancer prognosis. In this context, we investigated the effect of chronic stress on tumor progression taking into account both its influence on the immune system and on tumor biology. Furthermore, we analyzed the action of selective serotonin reuptake inhibitors, fluoxetine and sertraline, in these effects. For this purpose, C57BL/6J mice submitted or not to a chronic stress model and treated or not with fluoxetine or sertraline were subcutaneously inoculated with EL4 cells to develop solid tumors. Our results indicated that chronic stress leads to an increase in both tumor growth and tumor cell dissemination. The analysis of cell cycle regulatory proteins showed that stress induced an increase in the mRNA levels of cyclins A2, D1, and D3 and a decrease in mRNA levels of cell cycle inhibitors p15, p16, p21, p27, stimulating cell cycle progression. Moreover, an augment of mRNA levels of metalloproteases (MMP-2 and MMP-9), a decrease of inhibitors of metalloproteases mRNA levels (TIMP 1, 2, and 3), and an increase in migration ability were found in tumors from stressed animals. In addition, a significant decrease of antitumor immune response in animals under stress was found. Adoptive lymphoid cell transfer experiments indicated that the reduced immune response in stressed animals influenced both the tumor growth and the metastatic capacity of tumor cells. Finally, we found an important beneficious effect of fluoxetine or sertraline treatment on cancer progression. Our results emphasize the crucial role of the immune system in tumor progression under stress situations. Although a direct effect of stress and drug treatment on tumor biology could not be ruled out, the beneficial effect of fluoxetine and sertraline appears to be mainly due to a restoration of antitumor immune response.
format Artículo
author Di Rosso, María Emilia
Sterle, Helena Andrea
Cremaschi, Graciela A.
Genaro, Ana María
author_facet Di Rosso, María Emilia
Sterle, Helena Andrea
Cremaschi, Graciela A.
Genaro, Ana María
author_sort Di Rosso, María Emilia
title Beneficial effect of fluoxetine and dertraline on chronic stress-induced tumor crowth and cell dissemination in a mouse model of lymphoma : crucial role of antitumor immunity
title_short Beneficial effect of fluoxetine and dertraline on chronic stress-induced tumor crowth and cell dissemination in a mouse model of lymphoma : crucial role of antitumor immunity
title_full Beneficial effect of fluoxetine and dertraline on chronic stress-induced tumor crowth and cell dissemination in a mouse model of lymphoma : crucial role of antitumor immunity
title_fullStr Beneficial effect of fluoxetine and dertraline on chronic stress-induced tumor crowth and cell dissemination in a mouse model of lymphoma : crucial role of antitumor immunity
title_full_unstemmed Beneficial effect of fluoxetine and dertraline on chronic stress-induced tumor crowth and cell dissemination in a mouse model of lymphoma : crucial role of antitumor immunity
title_sort beneficial effect of fluoxetine and dertraline on chronic stress-induced tumor crowth and cell dissemination in a mouse model of lymphoma : crucial role of antitumor immunity
publisher Frontiers
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8672
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