Metastasis inhibition via epithelial-mesenchymal transition by RNA interference and metformin in mammary neoplasia

• Grant number: 12/14079-5
• Support Opportunities: Regular Research Grants
• Duration: October 01, 2012 - September 30, 2014
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Debora Aparecida Pires de Campos Zuccari
• Grantee: Debora Aparecida Pires de Campos Zuccari
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil

Abstract

The Epithelial-mesenchymal transition (EMT) is characterized by the change in mesenchymal to epithelial phenotype leads to loss or reduced expression of markers of epithelial cells such as E-cadherin and claudin, and increased expression of markers of mesenchymal cells such as n- cadherin and vimentin, as well as increased expression of the transcription factor twist. The EMT can be induced by extracellular matrix components and growth factors such as transforming growth factor beta (TGF-²), responsible for regulating cellular differentiation and proliferation, migration and apoptosis. The EMT starts with the transformation and differentiation of stem cells in breast cancer (BCSCs). Recent studies reproduced in vitro process of EMT in mammary epithelial cells generating cell BCSCs properties. In addition, a small subpopulation of tumor cells with the phenotype characteristic of stem cells (CD44 + / CD24-) are present in breast tumors. Currently, various tools of intervention have been employed to inhibit EMT and subsequent metastasis, such as the use of RNA interference (siRNA). For this purpose, recently emerged new research using metformin, a drug for type 2 diabetes, inhibiting the action of TGF-B in EMT and subsequent metastasis of breast cancer. The objective of this study is to identify markers associated with EMT, by immunofluorescence staining and RT-PCR, and prevent the process of metastasis of breast cancer through inhibition of TGF-² by siRNA technology and treatment with metformin in canine breast cancer cell lines and in animal model. The data obtained in this study will confirm the likely benefits of gene silencing and metformin as therapeutic agents in the treatment of breast cancer, reducing the occurrence of metastases and thus contributing to a better prognosis for patients with breast cancer. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LEONEL, CAMILA; FERREIRA, LIVIA CARVALHO; BORIN, THAIZ FERRAZ; MOSCHETTA, MARINA GOBBE; FREITAS, GABRIELA SCAVACINI; HADDAD, MICHEL RAINERI; DE CAMARGOS PINTO ROBLES, JOAO ANTONIO; PIRES DE CAMPOS ZUCCARI, DEBORA APARECIDA. Inhibition of Epithelial-mesenchymal Transition in Response to Treatment with Metformin and Y27632 in Breast Cancer Cell Lines. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, v. 17, n. 8, p. 1113-1125, 2017. (12/14079-5)