Biological significance of stress on the modulation of the tumor-stemness phenotype

• Grant number: 15/02498-1
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2015
• End date: May 31, 2017
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Vanessa Morais Freitas
• Grantee: Vanessa Morais Freitas
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Breast cancer is the second most deadliest cancer worldwide, as well as the most frequent and deadliest malignancy in the female population. Breast cancer is known to be highly heterogeneous and recent studies indicate that the poor prognosis associated with certain subtypes of breast cancer may be related to the higher proportion of cells with the tumor-stemness phenotype in these cases. The cancer stem cells (CSCs) are capable of self-renewal and differentiation, in addition to presenting high chemoresistance, hence often being associated with the process of tumor recurrence.The characteristic features of the tumor microenvironment include acidosis, hypoxia, nutrient deficiency and lack of adequate substrate. On the other hand, the in vitro model conventionally utilized for research on cancer does not faithfully reproduce the tumor microenvironment, once it presents a physiological pH, normoxia, and nutrient-enriched culture media, along with plastic-derived bidimensional substrates, which are chemically-treated to favor cell adhesion. In order to better comprehend the effect of the microenvironment on the behavior of tumor cells, we intend to perform biological assays in which tumor cells will be exposed to a multitude of stressful conditions, resulting in the death of non-adapted clones. We will evaluate the stemness phenotype through analysis of gene and protein expression, extracellular vesicle release, cellular anchorage-independent growth on agar gel, cell migration and cell invasion in vitro, as well as tumorigenic and metastatic potential in vivo. The generation of these stress-resistant clones likely enriched with cancer stem cells will help to increase our understanding regarding this disease and also to serve as a model for the development of new medicines capable of targeting the most aggressive tumors. (AU)

Scientific publications

(6)

(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)

NORIEGA-GUERRA, HEYDI; CRUZ, MARIO C.; RIBEIRO, PRISCILLA R. L.; STRNADEL, JAN; WAN, HUAWEI; KLEMKE, RICHARD L.; JAEGER, RUY G.; FREITAS, VANESSA M.. ADAMTS-1 disrupts HGF/c-MET signaling and HGF-stimulated cellular processes in fibrosarcoma. Experimental Cell Research, v. 363, n. 2, p. 271-282, FEB 15 2018. (10/07699-1, 15/02498-1, 12/24108-2)

SMUCZEK, BASILIO; SANTOS, EMERSON DE S.; SIQUEIRA, ADRIANE S.; PINHEIRO, JOAO J. V.; FREITAS, VANESSA M.; JAEGER, RUY G.. The laminin-derived peptide C16 regulates GPNMB expression and function in breast cancer. Experimental Cell Research, v. 358, n. 2, p. 323-334, SEP 15 2017. (15/02498-1, 15/03393-9)

SILVA, SUELY V.; LIMA, MAIRA A.; CELLA, NATHALIE; JAEGER, RUY G.; FREITAS, VANESSA M.. ADAMTS-1 Is Found in the Nuclei of Normal and Tumoral Breast Cells. PLoS One, v. 11, n. 10, OCT 20 2016. (13/01092-6, 15/02498-1, 15/09845-9, 12/10053-1, 10/07699-1, 15/19773-5)

LIMA RALPH, ANA CAROLINA; VALADAO, IURI CORDEIRO; CARDOSO, ELAINE CRISTINA; MARTINS, VILMA REGINA; SILVA OLIVEIRA, LUANDA MARA; ANDRADE FORELL BEVILACQUA, ESTELA MARIS; GERALDO, MURILO VIEIRA; JAEGER, RUY GASTALDONI; GOLDBERG, GARY S.; FREITAS, VANESSA MORAIS. Environmental control of mammary carcinoma cell expansion by acidification and spheroid formation in vitro. SCIENTIFIC REPORTS, v. 10, n. 1, DEC 15 2020. (19/00496-2, 15/02498-1)

LONGHI, MARIANA TAMAZATO; MAGALHAES, MAGNA; REINA, JEFFREY; FREITAS, VANESSA MORAIS; CELLA, NATHALIE. EGFR Signaling Regulates Maspin/SerpinB5 Phosphorylation and Nuclear Localization in Mammary Epithelial Cells. PLoS One, v. 11, n. 7, JUL 22 2016. (13/00815-4, 15/02498-1, 10/07699-1)

VALADAO, IURI C.; RALPH, ANA CAROLINA L.; BORDELEAU, FRANCOIS; DZIK, LUCIANA M.; BORBELY, KAREN S. C.; GERALDO, V, MURILO; REINHART-KING, CYNTHIA A.; FREITAS, VANESSA M.. High type I collagen density fails to increase breast cancer stem cell phenotype. PeerJ, v. 8, MAY 12 2020. (15/02498-1)