Study of the relative frequency and participation of cancer stem cells subpopulations in the process of metastasis of Oral Squamous Cell Carcinoma

• Grant number: 15/00101-7
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): March 01, 2015
• Effective date (End): November 30, 2016
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Camila de Oliveira Rodini Pegoraro
• Grantee: Nathália Martins Lopes
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
• Associated research grant: 13/07245-9 - Investigation of the role of cancer stem cells and microenvironment on epithelial-to-mesenchymal transition, invasion and metastasis in oral squamous cell carcinoma, AP.JP

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most common malignant neoplasms of the head and neck and still results in great morbidity and mortality annually. The presence of metastasis in cervical lymph nodes is the most significant prognostic factor. Studies have associated the mechanisms of tumor progression, recurrence and metastasis with the presence and maintenance of cancer stem cells (CSC), as well as the activation of the epithelial-mesenchymal (EMT) program. Still, recent evidences have shown that there is a link between CSC and EMT in such way that the CSC corresponds to the most migratory and highly metastatic cellular subpopulation when compared to other cell subpopulations within the tumor. Therefore, the purpose of this study is to contribute to the comprehension of the biological behavior of tumor epithelial cells able to invade the underlying connective tissue, reach the blood and lymph circulation and generate metastasis, searching for possible biological markers of tumor invasiveness in OSCC with clinical application. In view of that, the expression levels of genes related with CSC (CD44, P75NGFR, BMI-1 and ALDH-1) and EMT (vimentin, SNAIL, AXL, E/N-cadherin and TWIST1) phenotypes will be comparatively evaluated by qPCR on SCC-9 SCC cell line, the correspondent metastatic cell line SCC-9 LN1 obtained after in vivo tumorigenesis assays, as well as on human palate epithelial cells (HPEC) generated by primary culture. Protein expression levels of some selected CSC and EMT markers will be further evaluated by means of immunofluorescence. Additionally, SCC-9 and SCC-9 LN1 cell lines will be analyzed regarding their capacity to form tumor colonies and spheres, as part of the evaluation of the presence and proportion of cells with properties of CSC within the whole tumor population. At the end, we believe that the results might contribute to the knowledge about the mechanisms that regulate OSCC metastasis and might reveal new possible therapeutic targets for tumor invasion inhibition.

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)

RODINI, CAMILA OLIVEIRA; LOPES, NATHALIA MARTINS; LARA, VANESSA SOARES; MACKENZIE, IAN CAMPBELL. Oral cancer stem cells - properties and consequences. Journal of Applied Oral Science, v. 25, n. 6, p. 708-715, NOV-DEC 2017. (13/07245-9, 15/00101-7)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

LOPES, Nathália Martins. Study of the relative frequency and participation of cancer stem cells subpopulations in the process of metastasis of oral squamous cell carcinoma. 2016. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Odontologia de Bauru (FOB/SDB) Bauru.