Functions of progesterone and ADAMTS 1 protease in the migration of cells derived from ovarian cancer

• Grant number: 15/19773-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2016
• End date: February 01, 2020
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Vanessa Morais Freitas
• Grantee: Maíra de Assis Lima
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 18/19813-5 - Function of progesterone and ADAMTS 1 in the migration of cells derived from ovarian cancer, BE.EP.DR

Abstract

Ovarian carcinoma is the leading cause of gynecological neoplastic death, being associated primarily with deregulation of sex hormones. The progression of cancer depends not only on abilities acquired by cancer cells, but also the interaction between cells and their microenvironment. The components of the extracellular matrix (ECM) are involved in several aspects of tumor biology, providing a solid support for cells, cytokines and growth factors. ECM components are cleaved by proteases during physiological and pathological processes; it is essential for the migratory and invasive ability of cells. ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs or adamalysin-thrombospondin) are secreted proteases involved in collagen processing, cleavage of the proteoglycan matrix and angiogenesis. Our previous results demonstrated that progesterone increases gene and protein levels of ADAMTS 1 and 4 and reduces the migratory and invasive ability of NIH-OVCAR-3 and ES-2 cells compared the cells without treatment. Our goal here is to investigate the mechanisms by which progesterone leads to decreased of invasion and migration of NIH-OVCAR-3 and ES-2 cells and if ADAMTS 1 is involved in this process. For this purpose cells derived from ovarian cancer will have levels of ADAMTS 1 modulated (either with increase or decrease), and will be compared to parental cells. In addition, cells with modulated levels of ADAMTS1 gene and parental cells will experienced treatment with progesterone, and compared with untreated cells. Thus, we are going to study progesterone and ADAMTS 1 roles in the activation of signaling pathways that trigger changes in cell migration and invasion and how they act on invadopodia formation. (AU)

Scientific publications

(4)

(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)

LIMA, MAIRA DE ASSIS; DA SILVA, SUELY VIEIRA; SERRANO-GARRIDO, ORLANDO; HUELSEMANN, MAREN; SANTOS-NERES, LUANA; CARLOS RODRIGUEZ-MANZANEQUE, JUAN; HODGSON, LOUIS; FREITAS, VANESSA M.. Metalloprotease ADAMTS-1 decreases cell migration and invasion modulating the spatiotemporal dynamics of Cdc42 activity. CELLULAR SIGNALLING, v. 77, JAN 2021. (15/19773-5, 18/19813-5, 18/05566-6)

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)

LIMA, M. A.; SILVA, S. V.; FREITAS, V. M.. Progesterone and protease ADAMTS 1 regulating tumor cells migration and invasion.. MOLECULAR BIOLOGY OF THE CELL, v. 29, n. 26, p. 2-pg., 2018-12-15. (15/19773-5, 18/05566-6)

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)

Academic Publications

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

LIMA, Maíra de Assis. Progesterone and ADAMTS-1 effects on ovarian cancer cells migration.. 2020. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.