CRIPTO1/3 MODULATES INVASION OF TROPHOBLAST HTR8/SV-NEO CELL LINEAGE

BANDEIRA CARLA; HOSHIDA MARA; KNOFLER MARTIN; PANZETTA- DUTARI GRACIELA; GENTI DE RAIMONDI SUSANA; RIDANO MAGALI; FRANCISCO ROSSANA; BEVILACQUA ESTELA

Queensland

Congreso; IFPA; 2015

Background. CRIPTO1 (CR1) is a member of the epidermal growthfactor family with specific functions during embryo development (coreceptorfor Nodal in the establishment of embryonic axis) and tumor(found at high levels in colon, breast, lung, testis, ovary, pancreas andstomach cancer cells). In normal adult tissues, it has been found inthe mammary glands during pregnancy and lactation. Trophoblastdevelopment resembles in many ways the oncogenic process; however,as well as in tumors, the exact regulatory mechanisms thatregulate cell invasion are not clear. Previous studies have shownimmunolocalization of CR1 at term healthy placenta and in placentaswith invasiveness disorders, which suggested important roles in thisbiological process.Objectives. To determine the role of CR1 and CR3 in human trophoblasticcell invasion.Material & methods. Gene and protein levels were determined by RT-PCRand immunolocalization and Western blotting in first and third trimesterEVT cells and in HTR8/SV-neo cells. Recombinant CRIPTO was used toevaluate the role of this growth factor in invasion and migration activity ofthe trophoblast cell lineage by using transwell/matrigel assays. InterferingRNA strategy was employed to determine the role of CR1 in HTR-8/SVneocell invasion.Results. CR3 were highly expressed in EVT and HTR8 cells, whereas CR1was only found in third trimester EVT cells. Recombinant CRIPTO signifi-cantly increased the expression of CRIPTO and invasion and migration ofHTR8 cells in a time- and concentration-dependent manner. InterferingRNA specific for CRIPTO significantly decreased migration and invasionactivities of HTR-8/SVneo cells. These findings suggest that CR3 participatesin the trophoblast cell invasion-associated pathways. This studycontributes to the identification of factors associated with trophoblastinvasiveness in normal and pathological conditions. Supported by CAPES,CNPq & FAPESP