INVESTIGADORES
CROCI RUSSO Diego Omar
artículos
Título:
GLYCOSYLATION-DEPENDENT LECTIN-RECEPTOR INTERACTIONS PRESERVE ANGIOGENESIS IN ANTI-VEGF REFRACTORY TUMORS
Autor/es:
CROCI DO; CERLIANI JP; DALOTTO MORENO T.; MENDEZ HUERGO SP; ID. MASCANFRONI; DERGAN DYLON S.; M. A. TOSCANO; CARAMELO JJ,; GARCIA-VALLEJO JJ; J. OUYANG; MESRI EA; JUNTTILA MR; BAIS C; MA. SHIPP; M. SALATINO; G.A. RABINOVICH
Revista:
CELL
Editorial:
CELL PRESS
Referencias:
Lugar: United States; Año: 2014 p. 744 - 758
ISSN:
0092-8674
Resumen:
The clinical benefit conferred by vascular endothelial
growth factors (VEGF)-targeted therapies is variable,
and tumors from treated patients eventually reinitiate
growth. Here, we identify a glycosylation-dependent
pathway that compensates for the absence of
cognate ligand and preserves angiogenesis in
response to VEGF blockade. Remodeling of the
endothelial cell (EC) surface glycome selectively
regulated binding of galectin-1 (Gal1), which upon
recognition of complex N-glycans on VEGFR2,
activated VEGF-like signaling. Vessels within anti-
VEGF-sensitive tumors exhibited high levels of
a2-6-linked sialic acid, which prevented Gal1 binding.
In contrast, anti-VEGF refractory tumors secreted
increased Gal1 and their associated vasculature dis-
played glycosylation patterns that facilitated Gal1-EC
interactions. Interruption of b1-6GlcNAc branching in
ECs or silencing of tumor-derived Gal1 converted
refractory into anti-VEGF-sensitive tumors, whereas
elimination of a2-6-linked sialic acid conferred resis-
tance to anti-VEGF. Disruption of the Gal1-N-glycan
axis promoted vascular remodeling, immune cell
influx and tumor growth inhibition. Thus, targeting
glycosylation-dependent lectin-receptor interactions
may increase the efficacy of anti-VEGF treatmen