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Chemokine functions in collective cancer cell invasion: induction, guidance and systemic dissemination

Obiettivo

Cancer progression recapitulates, in part, ill-fated morphogenesis, including single-cell and collective cell migration and associated invasive growth, metastasis and poor prognosis of cancer disease. Chemokines and their receptors enhance cancer progression, by supporting both cancer invasion and proliferation. Previous studies have addressed chemokine function on individual cancer cell functions with emphasis on in vitro effects, yet their contribution to in vivo growth and collective cancer invasion remain unclear. In this project, using state-of the art in vitro and in vivo models, the impact of chemokines and chemokine receptor expression and function on collective cancer invasion and leader-cell function will be addressed. Candidate chemokines identified through in vitro invasion studies will be tested for their ability to guide collective cancer invasion in vivo, using orthotopic 3D matrix cultures and down modulation or overexpression of individual or multiple chemokine receptors. Chemokine-driven collective invasion will be monitored in orthotopic tumor xenografts in nude mice or zebrafish embryos, monitored by intravital microscopy. By inhibiting and/or overexpressing defined chemokine receptor pairs, chemokine-mediated cell sorting and leader-cell function will be monitored. This project will show new functions of chemokine signaling in collective cancer cell invasion, in reminiscence of multicellular movements during embryonic development.

Invito a presentare proposte

FP7-PEOPLE-2010-IEF
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Coordinatore

STICHTING RADBOUD UNIVERSITEIT
Contributo UE
€ 176 185,60
Indirizzo
HOUTLAAN 4
6525 XZ Nijmegen
Paesi Bassi

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Regione
Oost-Nederland Gelderland Arnhem/Nijmegen
Tipo di attività
Higher or Secondary Education Establishments
Contatto amministrativo
Maarten Van Langen (Mr.)
Collegamenti
Costo totale
Nessun dato