SEROTONIN INCREASES AGGRESSIVENESS IN BREAST CANCER IN A IN VITRO MODEL

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  • Presentation type: DR - Doctoral Student
  • Track: 3. Molecular Biology
  • Keywords: serotonin; Breast cancer; progression; aggressiveness;

Authors:

  • 1 Universidade Federal do Rio de Janeiro
  • 2 Universidade Federal do Estado do Rio de Janeiro
  • 3 University of Rio de Janeiro

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Abstract

INTRODUCTION AND OBJECTIVES: Serotonin (5-HT) is a bioactive monoamine present in human body. Classically, 5-HT is known for behavioral patterns controlled by central nervous system like mood, hunger and happiness. However, also has its functions in the peripheral system as blood clotting, tissue regeneration and peristaltic moviments. In breast tissue, 5-HT is described as responsible for mammary development and involution during lactation. This mitogenic effect of 5-HT is important for cancer as it can increase the aggressiveness and progression of the disease. Because of this, our team is investigating the effect of 5-HT in tumoral and non-tumoral breast cell lines, to elucidate its mechanisms in breast cancer disease. MATERIAL AND METHODS: For this we used 3 different cell lines, MCF10A, human epithelial non tumor cell line, MCF7, human breast cancer cell, with low metastatic potency, and MDAmb231, human breast cancer cell, with high metastatic potency. All cell lines were treated with 10 µM 5-HT, and were analyzed by qPCR, flow cytometry and microscopy. RESULTS AND CONCLUSION: Our results showed that the 5-HT-treated MCF7 and MDAmb231 cell lines (both tumoral) proliferated more in 24h, compared with the control condition. While, non-tumor cell line, MCF10A, had a reduction of number of living cells after the same time of treatment. To confirm this result, we observed the migration capability of these cells, and our experiment showed that MCF7 and MDAmb231 migrated more after 5-HT treatment, which was not observed in MCF10A cell line. Concomitantly, we analyzed hormonal receptors, which are breast cancer aggressiveness markers, and 5-HT augmented progesterone receptor (PGR) and epidermal factor receptor (HER-2) in MCF10A, in time that reduced estrogen receptor (ER), PGR and Her-2 in MCF7 and did not alter these receptors in MDAmb231. This shows that 5-HT is able to change the molecular profile of the MCF7 cell line from a Luminal A type to a more aggressive model such as the triple negative. Also, we analyzed epithelial-mesenchymal markers in MCF7 cell line, and 5-HT enhanced MMP9 enzyme, SNAIL and TWIST transcription factors mRNA, and reduced E-cadherin protein mRNA, shows that this mechanism of aggressiveness is initiated by 5-HT. Collectively, these results indicate us the differential ability of 5-HT to increase aggressiveness in breast cancer cell lines, do not exerting it in non-tumor cell line.

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Author

Larissa Paixão

Olá, Pedro. Obrigada pelo elogio.

Sim, analisamos a expressão proteica dos receptores de 5HT nestas linhagens no nosso trabalho publicado em 2020 (SOLA-PENNA et al; doi:10.1038/s41416-019-0640-1). Vimos que a linhagem MCF10A tem o receptor da família 7 expresso, a linhagem MCF7 tem o receptor 2C expresso, e a linhagem MDAmb231 tem ambos os receptores expressos.

No meu trabalho de mestrado, comparamos os efeitos da 5HT em linhagens in vitro com tumores de xenoenxerto in vivo desenvolvidos em camundongos tratados com 40mg/kg de Fluoxetina (SSRI). Nestas condições, observamos que os animais tratados tinham maior volume tumoral assim como aumento do lactato produzido após tratamento, igual observamos na linhagem MCF7 tratada com 5HT (SOLA-PENNA et al, 2020). Também avaliamos o conteúdo de mRNA de SERT neste trabalho e não observamos alterações em nenhum dos modelos desenvolvidos.

Não avaliamos nenhum processo envolvendo serotonylation por enquanto, no entanto procuraremos investigar.

Atenciosamente,

Larissa Paixão.

Author

Larissa Paixão

Olá, Leonardo. Obrigada pelos elogios.

No momento, estamos no processo de avaliar a expressão proteica dos marcadores de EMT, a fim de complementar os resultados apresentados. Também estamos investigando a capacidade da 5HT aumentar a resistência ao tratamento com Tamoxifeno, uma vez que o principal mecanismo de ação dele é o receptor de estrogênio, que é reduzido pelo tratamento com a 5HT.

Att.,

Larissa Paixão.