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In vivo studies on the effects of ²3 integrin subunit silencing in murine breast cancer

Grant number: 23/14732-5
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2023
Effective date (End): November 30, 2024
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Heloisa Sobreiro Selistre de Araújo
Grantee:Ana Carolina Woord
Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Breast cancer is a heterogeneous disease with a high incidence in the femalepopulation and with the highest mortality rate among women in Brazil. Tumors thatexpress some type of hormone receptor respond favorably to existing therapies;however, triple-negative tumors, which do not contain them, are difficult to treat. Theinsufficient response of triple-negative tumors to therapeutic resources and thesubsequent resistance developed by the tumors contribute to an unfavorable prognosisfor patients. A supporting target to traditional therapies are integrins, importantheterodimers for adhesion of tumor cells to the extracellular matrix (ECM) and inintracellular signaling. Integrins play a fundamental role in the epithelial-mesenchymaltransition, ensuring tumor survival and assisting in its metastasis process. Specifically,±v²3 integrin recognizes RGD motifs and is of great importance in tumor progression,acting on cell migration and activation of the VEGF/VEGFR2 axis, resulting inangiogenesis. Disintegrins that bind to ±v²3 integrin, such as DisBa-01, act to inhibitpro-tumor behaviors such as invasion, metastasis and adherence to ECM components.The present study aims to evaluate the impacts of silencing the ²3 subunit of murine4T1BM2 cells on tumor progression in an in vivo model, more specifically onmetastatic activity and angiogenesis, in comparison with a control group, in search ofnew therapeutic targets for the treatment of breast tumors that do not respond well totraditional therapies.

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