In vitro and in vivo characterization of immunomarkers for cancer stem cells in a human breast cancer cell line

• Grant number: 11/11609-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): March 01, 2012
• Effective date (End): July 31, 2015
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: André Almeida Schenka
• Grantee: Valéria Barbosa de Souza
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Stem cells (SCs) are characterized by the capacity for self-renewal and multilineage differentiation and participate actively in countless physiologic and pathologic processes. Recently, in a new paradigm for carcinogenesis, SCs have been regarded as responsible for the origin, morphologic heterogeneity and self-renewal of malignant neoplasms. In support of this theory, it has been detected in most solid neoplasms a subpopulation of cells bearing functional and phenotypic resemblance to SCs, which was designated as cancer stem cells (CSCs). CSCs have been associated to primary therapeutic failure and long term tumor recurrences, and are now regarded as major targets in both pathophysiologic and pharmacologic studies. Currently, the main obstacles to these CSC studies are: dificulties concerning detection methods and scarcity of in vivo CSC-specific models. In this context, the present study aims to investigate and validate a large panel of putative CSC immunomarkers, using a well known malignant cell line derived from a mammary carcinoma - MCF-7, AU565 and HCC1428. We focus on questions such as reproducibility, sensitivity and specificity, according to the technique of immunophenotyping and the experimental approach (in vitro vs. in vivo). In addition, it will be assessed a possible association between these markers and specific molecules bearing predictive value. For that matter, the immunoexpression of CSC will be assessed by immunocytochemical methods and flow cytometry in MCF-7, AU565 and HCC1428 cells obtained from cell culture and xenotransplants induced on SCID/SCID mice. Latter, the expression of different CSC markers will be correlated to the positivy for predictive markers (C-erb-B2, MDR1, ABCG2 e ABCA3), by linear regression. We hope to contribute to the validation of CSC detection methods with greater accuracy and reproducibility, in order to foment pathophysiology and pharmacology studies on breast cancer. (AU)

Academic Publications

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

SOUZA, Valéria Barbosa de. Influence 'in vitro' and 'in vivo' contexts on the expression of cancer stem cell markers in breast cancer - derived cell lines. 2015. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.