Protease ADAMTS1 influencing breast cancer behavior and microenvironment

• Grant number: 10/07699-1
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: October 01, 2010
• End date: September 30, 2014
• 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
• Associated researchers: Fernando Augusto Soares ; Ruy Gastaldoni Jaeger
• Associated research grant(s): 14/18936-5 - 2014 ASCB/IFCB Meeting, AR.EXT
• Associated scholarship(s): 13/01092-6 - Influence of steroid hormones in expression levels and location of ADAMTS-1, 4 and 9 in cells derived from ovarian tumors, BP.MS; 12/24108-2 - Role of ADAMTS-1 in local and systemic invasion of fibrosarcoma cells, BP.DD; 12/10053-1 - Influence of estrogens, progestins and androgens on ADAMTS-1 levels and distribution in normal and tumoral breast cells, BP.MS; 11/09472-7 - AHNAK regulates formation and exchange of extracellular vesicles between breast tumor cells and fibroblasts, BP.DR; 11/00650-0 - Influence of estrogens, progestins and androgens in ADAMTS-1 levels in breast cancer cells., BP.IC

Abstract

We have been studying the role of different proteases in tumor biology (Franca et al. 2001; Freitas & Jaeger 2002; Freitas et al. 2004; Pinheiro et al. 2004; Freitas et al. 2007; Morais Freitas et al. 2007; Freitas et al. 2008; Gama-de-Souza et al. 2008; Jaeger et al. 2008; Nascimento et al. 2010). Previous results showed that ADAMTS-1 regulates migration of breast cancer cells in culture. This project will extend our previous results on the role played by ADAMTS-1 in breast cancer biology. The in vivo expression of this protease will be assessed in different breast tumors. Clinical-pathological data and survival curves will be obtained, in order to compare tumors with ADAMTS-1 expressed or not. We will also establish an in vitro model to study regulatory mechanisms underlying ADAMTS-1 effects in tumor cells. Mammary cell lines (MCF10A, MCF-7, and MDA-MB-231) will be treated by hormones and growth factors related to breast cancer, such as estrogen, progesterone and androgen. After treatment, ADAMTS-1 levels (protein and mRNA) will be evaluated. We will also investigate whether ADAMTS-1 would influence receptors for estrogen, progesterone and androgens. Finally, the role played by ADAMTS-1 regulating tumor microenvironment will be addressed. This analysis will include following experimental conditions: 1) co-culture; 2) presence of ADAMTS-1 in matrices extracted from mammary cancer; 3) tumor cells with ADAMTS-1 silenced by siRNA and subjected to nude mice xenografts. (AU)

Scientific publications

(9)

(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)

BUONFIGLIO, DANIELLA C.; RAMOS-LOBO, ANGELA M.; FREITAS, VANESSA M.; ZAMPIERI, THAIS T.; NAGAISHI, VANESSA S.; MAGALHAES, MAGNA; CIPOLLA-NETO, JOSE; CELLA, NATHALIE; DONATO, JR., JOSE. Obesity impairs lactation performance in mice by inducing prolactin resistance. SCIENTIFIC REPORTS, v. 6, MAR 1 2016. (10/18086-0, 13/16374-7, 14/11752-6, 15/10992-6, 12/15517-6, 10/07699-1)

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)

SILVA, THAIOMARA A.; SMUCZEK, BASILIO; VALADAO, IURI C.; DZIK, LUCIANA M.; IGLESIA, REBECA P.; CRUZ, MARIO C.; ZELANIS, ANDRE; DE SIQUEIRA, ADRIANE S.; SERRANO, SOLANGE M. T.; GOLDBERG, GARY S.; et al. AHNAK enables mammary carcinoma cells to produce extracellular vesicles that increase neighboring fibroblast cell motility. ONCOTARGET, v. 7, n. 31, p. 49998-50016, AUG 2 2016. (13/07467-1, 11/09472-7, 15/00544-6, 10/07699-1)

LIMA, MAIRA ASSIS; DOS SANTOS, LILIANE; TURRI, JOSE ANTONIO; NONOGAKI, SUELY; BUIM, MARCILEI; LIMA, JOEMA FELIPE; VIANA PINHEIRO, JOAO DE JESUS; BUENO DE TOLEDO OSORIO, CYNTHIA APARECIDA; SOARES, FERNANDO AUGUSTO; FREITAS, VANESSA MORALS. Prognostic Value of ADAMTS Proteases and Their Substrates in Epithelial Ovarian Cancer. PATHOBIOLOGY, v. 83, n. 6, p. 316-326, 2016. (13/01092-6, 10/07699-1)

CAIRES-DOS-SANTOS, LIVIA; DA SILVA, SUELY V.; SMUCZEK, BASILIO; DE SIQUEIRA, ADRIANE S.; CRUZ, KAREN S. P.; BARBUTO, JOSE ALEXANDRE M.; AUGUSTO, TAIZE M.; FREITAS, VANESSA M.; CARVALHO, HERNANDES F.; JAEGER, RUY G.. Laminin-derived peptide C16 regulates Tks expression and reactive oxygen species generation in human prostate cancer cells. Journal of Cellular Physiology, v. 235, n. 1, JUN 2019. (09/16150-6, 18/03528-0, 09/17336-6, 10/07699-1, 15/03393-9)

FREITAS, VANESSA M.; DO AMARAL, JONATAS BUSSADOR; SILVA, THAIOMARA A.; SANTOS, EMERSON S.; MANGONE, FLAVIA R.; PINHEIRO, JOAO DE JESUS; JAEGER, RUY G.; NAGAI, MARIA A.; MACHADO-SANTELLI, GLAUCIA MARIA. Decreased expression of ADAMTS-1 in human breast tumors stimulates migration and invasion. Molecular Cancer, v. 12, JAN 5 2013. (06/01026-0, 10/07699-1)

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)

LIMA, MAIRA A.; SILVA, V, SUELY; JAEGER, RUY G.; FREITAS, VANESSA M.. Progesterone decreases ovarian cancer cells migration and invasion. Steroids, v. 161, SEP 2020. (18/19813-5, 18/05566-6, 15/19773-5, 10/07699-1)