Scholarship 24/10239-5 - Neoplasias do colo uterino, Imunomodulação - BV FAPESP
Advanced search
Start date
Betweenand

Effects of chronic butyrate exposition on the cervical cancer tumor microenvironment.

Grant number: 24/10239-5
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Start date until: October 01, 2024
End date until: September 30, 2025
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Ana Paula Lepique
Grantee:Francisco Cândido do Nascimento Pombo
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cervical cancer is a tumor caused by the infection with Human Papiloma Virus (HPV), it hasa worldwide impact, while having a stronger presence in developing countries. Although theHPV infection is a fundamental factor for the developing of tumors, it has been shown thatchanges in the genital microbiota can take part in this process. Literature data have shownthat the reduction of bacteria from the Lactobacillus genus, which produce lactate, and theincrease of short-chain fatty acids-producing anaerobic bacteria are alterations associatedwith the development of this type of cancer. One of these fatty acids is butyrate, a moleculecapable of activating GPR41, GPCR43, and GPR109A receptors and inhibiting histonedeacetylase (HDAC) activity. Given the broad role of HDAC in epigenetic control, it is notsurprising that studies show butyrate can exert significant changes in cell cycle, cellularmetabolism, and differentiation of immune and tumor cells, although the findings are oftencontradictory. Such alterations can play a role both pro-tumoral (immunosuppression) andantitumoral (increasing apoptosis of tumor cells and enhancing macrophage microbicidalcapacity). Therefore, butyrate may have an effect both directly on tumor cells and on thetumor microenvironment. Again, the literature presents divergent data regarding the role ofbutyrate on cells within the tumor microenvironment. Preliminary data from our laboratoryconfirm that butyrate is capable of inhibiting proliferation and inducing death ofimmortalized keratinocytes, even when they express HPV oncogenes. Thus, we are workingunder the hypothesis that butyrate may have a dual therapeutic role against cervical cancer:2inducing death of tumor cells and simultaneously activating cytotoxic mechanisms inmacrophages. Our objective will be to test this hypothesis using co-cultures of tumor cellsand immortalized cells with primary macrophages. We hope to provide further insightsthrough well-controlled experiments in this area of cervical cancer research. Additionally, ifour hypothesis proves correct, we could potentially have a therapeutic tool against this typeof cancer.

News published in Agência FAPESP Newsletter about the scholarship:
More itemsLess items
Articles published in other media outlets ( ):
More itemsLess items
VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)

Please report errors in scientific publications list using this form.