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Trophoblast Invasion: New Insights into Cancer Metastasis using Human Placenta

21st national competition for scientific and technical research

Intercellular Dialogue and Interactome: Pathological Implications

Senior Researcher : Vicente Pérez García

Research Centre or Institution : Centro de Investigación Príncipe Felipe

Abstract

The placenta is a transient organ that connects the embryo to the mother during pregnancy and mediates nutrient and oxygen supply to sustain normal growth. Hence, the placenta orchestrates developmental outcomes and fetal growth. Full functionality of the placenta depends on the earliest steps during placentation when trophoblast cells, the building block of the placenta, invade into the endometrium to establish the definitive maternal-fetal interface. Several pregnancy complications such as miscarriage and preeclampsia are caused by defects in the process of trophoblast invasion. Despite extensive research on placental development, the precise molecular mechanisms that regulate correct trophoblast differentiation and invasion are poorly understood.

Intriguingly, trophoblast cells share key similarities with carcinomas which have their origin in epithelial tissues. These similarities include the ability to invade healthy tissues, the formation of new vessels, and the promotion of an immunotolerant environment. A key biological question remains: do tumour cells repurpose the same genes and mechanisms that are critical for trophoblast invasion?

INVADE will test the hypothesis that trophoblast and cancer cells exploit similar molecular mechanisms that endow them with their proliferative and invasive properties. We will use CRISPR/Cas9 genome editing technology to manipulate human trophoblast stem cells, cancer cells, and organoids to:

1) Identify the molecular signatures characteristic of human invasive placental cells.

2) Unravel the common molecular pathways between trophoblast invasion and cancer metastasis. Results of INVADE will provide fundamental insights into the cellular invasive mechanisms that coordinate human placentation and the potential implication of these same mechanisms in tumour metastasis. The identification of key placental strategies that regulate trophoblast invasion will open new avenues towards the development of novel targets for placental disorders as well as cancer therapy.

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