TY - JOUR
T1 - Vinblastine inhibits the angiogenic response induced by adrenomedullin in vitro and in vivo
AU - Ribatti, Domenico
AU - Guidolin, Diego
AU - Conconi, Maria Teresa
AU - Nico, Beatrice
AU - Baiguera, Silvia
AU - Parnigotto, Pier Paolo
AU - Vacca, Angelo
AU - Nussdorfer, Gastone Giovanni
PY - 2003/9/25
Y1 - 2003/9/25
N2 - Adrenomedullin (ADM) is protumorigenic by stimulating tumor cell growth and angiogenesis. In this context, ADM is identified as a novel target for antiangiogenic therapy. In this study, we addressed the possibility that vinblastine (VBL), as demonstrated in other experimental conditions, may act as an angiostatic molecule in the angiogenic response induced by ADM in two assays, such as Matrigel tube formation in vitro and angiogenesis in the chick embryo chorioallantoic membrane (CAM) in vivo. When tested on Matrigel, ADM caused a morphogenetic effect. In fact, endothelial cells spread and aligned with each other to form branching anastomosing tubes with multicentric junctions that gave rise to a meshwork of capillary-like structures. When ADM was administered in the presence of VBL, the capillary-like tubes were interrupted, most cells were spherical, either isolated or aggregated in small clumps. In the CAM assay, ADM induced a strong angiogenic response, which was counter-acted by the treatment with VBL. Overall, these observations implicate ADM as a promoter of tumor growth and a possible target for anticancer strategies, such as the use of VBL at very low, nontoxic doses. Nevertheless, the antiangiogenic acitivity of low-dose VBL deserves further investigation, alone or together with other antiangiogenic agents for the treatment of tumors characterized by enhanced angiogenesis.
AB - Adrenomedullin (ADM) is protumorigenic by stimulating tumor cell growth and angiogenesis. In this context, ADM is identified as a novel target for antiangiogenic therapy. In this study, we addressed the possibility that vinblastine (VBL), as demonstrated in other experimental conditions, may act as an angiostatic molecule in the angiogenic response induced by ADM in two assays, such as Matrigel tube formation in vitro and angiogenesis in the chick embryo chorioallantoic membrane (CAM) in vivo. When tested on Matrigel, ADM caused a morphogenetic effect. In fact, endothelial cells spread and aligned with each other to form branching anastomosing tubes with multicentric junctions that gave rise to a meshwork of capillary-like structures. When ADM was administered in the presence of VBL, the capillary-like tubes were interrupted, most cells were spherical, either isolated or aggregated in small clumps. In the CAM assay, ADM induced a strong angiogenic response, which was counter-acted by the treatment with VBL. Overall, these observations implicate ADM as a promoter of tumor growth and a possible target for anticancer strategies, such as the use of VBL at very low, nontoxic doses. Nevertheless, the antiangiogenic acitivity of low-dose VBL deserves further investigation, alone or together with other antiangiogenic agents for the treatment of tumors characterized by enhanced angiogenesis.
KW - Adrenomedullin
KW - Angiogenesis
KW - Antiangiogenesis
KW - Chorioallantoic membrane
KW - Matrigel
KW - Vinblastine
UR - http://www.scopus.com/inward/record.url?scp=0142135498&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0142135498&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1206789
DO - 10.1038/sj.onc.1206789
M3 - Article
C2 - 14508526
AN - SCOPUS:0142135498
VL - 22
SP - 6458
EP - 6461
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 41
ER -