INTEGRIN ALPHA(V)BETA(3) ANTAGONISTS PROMOTE TUMOR-REGRESSION BY INDUCING APOPTOSIS OF ANGIOGENIC BLOOD-VESSELS
INTEGRIN ALPHA(V)BETA(3) ANTAGONISTS PROMOTE TUMOR-REGRESSION BY INDUCING APOPTOSIS OF ANGIOGENIC BLOOD-VESSELS
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DOI：
10.1016/0092-8674(94)90007-8
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发表时间：
1994-12-30
期刊：
影响因子：
64.5
通讯作者：
CHERESH, DA
中科院分区：
文献类型：
--
作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
单次血管内注射整合素α (v) β(3)的环状肽或单克隆抗体拮抗剂可破坏鸡绒毛膜尿囊膜（CAM）上正在进行的血管生成。这导致移植到CAM上的组织学上不同的人类肿瘤迅速消退。肿瘤或细胞因子诱导血管生成促进血管细胞进入细胞周期和整合素α (v) β的表达(3)。在血管生成开始后，这种整合素的拮抗剂诱导增殖的血管生成血管细胞凋亡，使先前存在的静止血管不受影响。因此，我们证明整合素α (v) β(3)的结扎对于新形成的血管的存活和成熟是必需的，这是肿瘤增殖所必需的事件。
A single intravascular injection of a cyclic peptide or monoclonal antibody antagonist of integrin alpha(v) beta(3) disrupts ongoing angiogenesis on the chick chorioallantoic membrane (CAM). This leads to the rapid regression of histologically distinct human tumors transplanted onto the CAM. Induction of angiogenesis by a tumor or cytokine promotes vascular cell entry into the cell cycle and expression of integrin alpha(v) beta(3). After angiogenesis is initiated, antagonists of this integrin induce apoptosis of the proliferative angiogenic vascular cells, leaving preexisting quiescent blood vessels unaffected. We demonstrate therefore that ligation of integrin alpha(v) beta(3) is required for the survival and maturation of newly forming blood vessels, an event essential for the proliferation of tumors.