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Massimiliano Mazzone
Vessel Branching Morphogenesis
VIB Vesalius Research Center, K.U.Leuven


PhD: Univ. of Torino, Torino, Italy, '07
Postdoc Fellow at VIB, Vesalius Research Center, Univ. of Leuven, Leuven, Belgium, '06-'09
VIB Group leader since 2009

e-mail
phone +32 16 34 61 76
ADDRESS

Current team members
Group leader: Massimiliano Mazzone
Postdoctoral scientists: Estelle Delamarre, Sandra Costa
Ph.D. Students: Mathias Wenes, Rodrigo Leite de Oliveira, Sofie Deschoenmaeker, Veronica Finisguerra
Support personnel: Jens Serneels

Keywords
endothelial cell - angiogenesis - cancer

Science
In contrast to our increasing understanding of how vessels sprout, little is known about how vessels regulate their shape and morphogenesis. Understanding the mechanisms underlying these processes is important, since vessel shape regulates its primary function, i.e. to supply oxygen to distant cells. In addition, in pathological conditions such as cancer and ischemic diseases, vessels are abnormal and dysfunctional, which impairs perfusion and oxygenation.
Recent evidence indicates that endothelial cells at the forefront of a sprouting vessel acquire a unique “tip cell” specification; this fate is distinct from the endothelial “stalk cell”, which trails behind the pioneering tip cell. However, much less attention has been paid to the more quiescent endothelial cell type in non-growing vessels, that survives for many years and maintains lumen patency; these cells form a tightly aligned, orderly shaped, smooth layer with a typical cobblestone appearance, comparable to the ‘phalanx’ formation of Greek Spartan soldiers.
Phalanx cells participate in the normalization of the endothelial cell layer, that allows vessels to readjust their shape, not numbers, to optimize oxygen supply when the latter is insufficient.
The research group of Massimiliano Mazzone will shed light into the genetic and molecular mechanisms that regulate the phalanx endothelial cell fate, with the overall aim to define alternative therapeutic opportunities to improve anti-cancer therapy as well as therapeutic angiogenesis for revascularization of ischemic tissues, largely unmet medical problems to date.

Press Releases
See also press release (12/02/2009): New strategy to combat cancer: streamlining blood vessel walls - based on a publication in Cell (Mazzone et al.Cell, 2009)


Selected Publications



Casazza A, Finisguerra V, Capparuccia L, Camperi A, Swiercz J, Rizzolio S, Rolny C, Christensen C, Bertotti A, Sarotto I, Risio M, Trusolino L, Weitz J, Schneider M, Mazzone M, Comoglio P, Tamagnone L
Sema3E-Plexin D1 signaling drives human cancer cell invasiveness and metastatic spreading in mice
J CLIN INVEST 120, 2684-98, 2010



Mazzone M, Dettori D, Leite de Oliveira R, Loges S, Schmidt T, Jonckx B, Tian Y, Lanahan A, Pollard P, Ruiz de Almodovar C, De Smet F, Vinckier S, Aragonés J, Debackere K, Luttun A, Wyns S, Jordan B, Pisacane A, Gallez B, Lampugnani M, Dejana E, Simons M, Ratcliffe P, Maxwell P, Carmeliet P
Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization
CELL 136, 839-51, 2009



Fischer C, Jonckx B, Mazzone M, Zacchigna S, Loges S, Pattarini L, Chorianopoulos E, Liesenborghs L, Koch M, De Mol M, Autiero M, Wyns S, Plaisance S, Moons G, Van Rooijen N, Giacca M, Stassen J, Dewerchin M, Collen D, Carmeliet P
Anti-PlGF Inhibits Growth of VEGF(R)-Inhibitor-Resistant Tumors without Affecting Healthy Vessels
CELL 131, 463-75, 2007



Mazzone M, Basilico C, Cavassa S, Pennacchietti S, Risio M, Naldini L, Comoglio P, Michieli P
An uncleavable form of pro-scatter factor suppresses tumor growth and dissemination in mice
J CLIN INVEST 114, 1418-32, 2004



Michieli P, Mazzone M, Basilico C, Cavassa S, Sottile A, Naldini L, Comoglio P
Targeting the tumor and its microenvironment by a dual-function decoy Met receptor
CANCER CELL 6, 61-73, 2004







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