Involvement of human PECAM-1 in angiogenesis and in vitro endothelial cell migration

Involvement of human PECAM-1 in angiogenesis and in vitro endothelial cell migration
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DOI:
10.1152/ajpcell.00524.2001
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发表时间:
2002-05-01
影响因子:
5.5
通讯作者:
DeLisser, HM
DeLisser, HM
中科院分区:
生物学2区
文献类型:
--
作者:
Cao, GY;O'Brien, CD;DeLisser, HM

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血小板内皮细胞粘附分子(PECAM)-1与血管生成有关,但许多问题仍未解决,包括人类PECAM-1 (huPECAM-1)在肿瘤血管生成中的独立参与及其参与血管形成的机制。我们报告了在移植于严重联合免疫缺陷小鼠的人皮肤中生长的肿瘤,针对huPECAM-1的抗体(不同时使用抗ve -钙粘蛋白抗体)降低了与肿瘤相关的人血管的密度,而不是小鼠血管的密度。抗hupecam -1抗体还能抑制人脐静脉内皮细胞(HUVEC)形成管,以及HUVEC通过matrigel包被滤膜或损伤单层细胞修复过程中的迁移。huPECAM-1参与这些过程的发现被证实,在细胞转染物中表达huPECAM-1诱导管形成和增强细胞运动性。这些数据为PECAM-1在人类肿瘤血管生成(独立于ve -钙粘蛋白)中的作用提供了证据,并表明在血管生成过程中,PECAM-1参与了内皮细胞运动和/或其随后组织成血管管所需的粘附和/或信号现象。
Platelet endothelial cell adhesion molecule (PECAM)-1 has been implicated in angiogenesis, but a number of issues remain unsettled, including the independent involvement of human PECAM-1 (huPECAM-1) in tumor angiogenesis and the mechanisms of its participation in vessel formation. We report for tumors grown in human skin transplanted on severe combined immunodeficiency mice that antibodies against huPECAM-1 (without simultaneous treatment with anti-VE-cadherin antibody) decreased the density of human, but not murine, vessels associated with the tumors. Anti-huPECAM-1 antibody also inhibited tube formation by human umbilical vein endothelial cells (HUVEC) and the migration of HUVEC through Matrigel-coated filters or during the repair of wounded cell monolayers. The involvement of huPECAM-1 in these processes was confirmed by the finding that expression of huPECAM-1 in cellular transfectants induced tube formation and enhanced cell motility. These data provide evidence of a role for PECAM-1 in human tumor angiogenesis (independent of VE-cadherin) and suggest that during angiogenesis PECAM-1 participates in adhesive and/or signaling phenomena required for the motility of endothelial cells and/or their subsequent organization into vascular tubes.