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

Grant number: 18/19813-5
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): March 01, 2019
Effective date (End): August 31, 2019
Field of knowledge:Biological Sciences - Biology
Principal Investigator:Vanessa Morais Freitas
Grantee:Maíra de Assis Lima
Supervisor: Louis Hodgson
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: Albert Einstein College of Medicine, United States  
Associated to the scholarship:15/19773-5 - Functions of progesterone and ADAMTS 1 protease in the migration of cells derived from ovarian cancer, BP.DR


The progression of cancer depends on the interaction between the cells and their microenvironment. ADAMTSs (adamalysin-thrombospondin) are secreted proteases dependent on Zn2+/Ca2+ and participate in many physiological and pathological processes. Progesterone increases ADAMTSs gene and protein expression and reduces the migratory and invasive capacity of the ovary cells when compared to untreated cells. We observed that 500 nM or 1 ¼M progesterone decrease the migration of the cells without affecting the viability and the use of RU486 recovered the migratory capacity. In ADAMTS-1 enriched medium, cells had a decrease in migration when compared to controls and, in this condition, progesterone was capable of reduced cell migration. However, ADAMTS-1 knockout prevented decrease in migration induced by progesterone. Using the G-LISA® series of Small G-Protein Activation Assays we measure the GTP form of small G-proteins from lysates of cells and we have been observed that progesterone treatment decreases the active form of Rho GTPase CDC42 relative to the untreated sample. Deleted ADAMTS-1 increased CDC42 activity relative to wild-type control; on the other hand ES-2 cells treated with ADAMTS-1-enriched medium had a decrease in CDC42 activation relative to cells treated with the control medium. CDC42 is a member of the p21 Rho family of small GTPases that has been found to be implicated in a variety of signaling events and cellular functions including cell polarity, re-organization of the cytoskeleton, transcription, proliferation, adhesion, migration and membrane trafficking. Our goal is to investigate if progesterone leads to decreased invasion and migration of ES-2 cells by CDC42 and whether ADAMTS-1 is involved in this process. Using a Cdc42 biosensor developed to detect the activity of endogenous Cdc42 in living cells, CDC42 activation will be measured on wild type or ovarian cells modulated to ADAMTS-1 in the absence or presence of progesterone. (AU)

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

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