Investigation of the role of cancer stem cells and microenvironment on epithelial-to-mesenchymal transition, invasion and metastasis in oral squamous cell carcinoma

• Grant number: 13/07245-9
• Support Opportunities: Research Grants - Young Investigators Grants
• Duration: February 01, 2015 - May 31, 2020
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Camila de Oliveira Rodini Pegoraro
• Grantee: Camila de Oliveira Rodini Pegoraro
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
• Associated researchers: Daniela Elena Costea ; Gustavo Pompermaier Garlet ; Ian Campbell Mackenzie ; Marcela Rodrigues de Camargo ; Oswaldo Keith Okamoto ; Vanessa Soares Lara
• Associated grant(s): 15/12894-1 - Multi-User Equipment approved in grant 2013/07245-9: BD FACSAria cell sorter with BD FACSAria ACDU and acessories, AP.EMU
• Associated scholarship(s): 19/05704-2 - Biological material collection, storing, processing and transport, BP.TT; 17/25022-8 - Investigation of amoeboid cells in Oral Squamous Cell Carcinoma and their participation on metastasis, BP.DR; 17/26567-8 - In vitro induction role of the epithelial-mesenchymal transition in cell lines of oral squamous cell carcinoma biological behavior, BP.IC; + associated scholarships 17/01212-2 - In vitro antitumor activity of Ganoderma Lucidum polysaccharide associated with 5-FU metronomic chemotherapy on stem cell of head and neck squamous cell carcinoma., BP.PD; 15/06945-2 - Differential and comparative immunohistochemical analysis between primary OSCC and corresponding metastatic lesions, BP.MS; 15/00101-7 - Study of the relative frequency and participation of cancer stem cells subpopulations in the process of metastasis of Oral Squamous Cell Carcinoma, BP.MS - associated scholarships

Abstract

Recent evidences has shown that there is a link between cancer stem cells (CSC) and the process of epithelial-to-mesenchymal transition (EMT), so that the CSCs are more migratory and have higher metastasizing potential compared to other cancer cells. It is also known that EMT is increased by hypoxia and by inflammatory cytokines, environmental influences common within the tumors. In view of that, the purpose of this study is to determine the factors influencing the behaviour of EMT-CSCs and investigate whether their molecular signature can be used for identification of biomarkers that can be used as prognostic factors or for the choice of treatment. For this purpose, different putative CSC (CD44, P75NGFR, BMI-1 and ALDH-1), EMT (vimentin, Snail, Axl, E/N-cadherin and Twist1), macrophages (CD68, CD163 and F4/80) and TGFB1 signaling markers will be evaluated by immunohistochemistry on primary OSCC and associated metastatic lymph nodes. CD44 and ESA expression levels will also be analyzed by flow cytometry on fresh tissue samples, and the data will be collectively associated with clinical and pathological parameters. Additionally, circulating tumor cells on peripheral blood of advanced OSCC patients will be isolated, quantified and characterized regarding their CSC and EMT phenotype. Lastly, the functional relationship between tumor-associated macrophages (TAM), CSC and EMT will be further investigated regarding the invasive capacity of different CSC subpopulations (EMT-CSC or non-EMT-CSC) isolated by cell sorting, by means of indirect co-culture and invasion assays. The role of cytokines released from TAM, as well as TGFB1, will be specifically evaluated by gene silencing or over expression studies. (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)

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)

AMOR, NADIA GHINELLI; BUZO, RODRIGO FONSECA; ORTIZ, RAFAEL CARNEIRO; LOPES, NATHALIA MARTINS; SAITO, LUCIANA MIELI; MACKENZIE, IAN CAMPBELL; RODINI, CAMILA OLIVEIRA. In vitro and in vivo characterization of cancer stem cell subpopulations in oral squamous cell carcinoma. JOURNAL OF ORAL PATHOLOGY & MEDICINE, v. 50, n. 1, SEP 2020. (13/07245-9)

ORTIZ, RAFAEL C.; LOPES, NATHALIA M.; AMOR, NADIA G.; PONCE, JOSE B.; SCHMERLING, CLAUDIA K.; LARA, VANESSA S.; MOYSES, RAQUEL A.; RODINI, CAMILA O.. CD44 and ALDH1 immunoexpression as prognostic indicators of invasion and metastasis in oral squamous cell carcinoma. JOURNAL OF ORAL PATHOLOGY & MEDICINE, v. 47, n. 8, p. 740-747, SEP 2018. (13/07245-9)