Trefoil peptides as proangiogenic factors in vivo and in vitro: implication of cyclooxygenase-2 and EGF receptor signaling
Trefoil peptides as proangiogenic factors in vivo and in vitro: implication of cyclooxygenase-2 and EGF receptor signaling
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DOI：
10.1096/fj.02-0201com
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发表时间：
2003-01-01
期刊：
影响因子：
4.8
通讯作者：
Emami, S
中科院分区：
文献类型：
--
作者：
Rodrigues, S;Van Aken, E;Emami, S
我们以前建立了三叶肽（TFFs）pS2，痉挛多肽，肠三叶因子参与细胞散射和浸润在肾脏和结肠癌细胞。使用绒毛膜尿囊膜（CAM）测定和管样结构的形成由人脐静脉内皮细胞（HUVEC）铺在基质胶基质上，我们在这里报告，TFFs是促血管生成因子。TFF的血管生成活性与血管内皮生长因子、瘦素和转化生长因子-α诱导的血管生成活性相当。CAM试验中pS2对血管生成的刺激被环氧合酶考克斯-2（NS-398）和表皮生长因子受体（EGF-R）酪氨酸激酶（ZD 1839）的药理学抑制剂阻断，但不依赖于KDR/Flk-1和血栓烷A2受体。与此相反，在HUVEC细胞中由pS2诱导的形态发生转换可以被特异性KDR七肽拮抗剂ATWLPPR和考克斯-2和EGF-R信号传导抑制剂抑制。这些结果暗示TFF在正常和病理生理过程期间新血管的形成中，所述正常和病理生理过程与消化道粘膜中的伤口愈合、炎症和癌症进展以及与TFF异常表达相关的其他人实体瘤有关。
We previously established that the trefoil peptides (TFFs) pS2, spasmolytic polypeptide, and intestinal trefoil factor are involved in cellular scattering and invasion in kidney and colonic cancer cells. Using the chorioallantoic membrane (CAM) assay and the formation of tube-like structures by human umbilical vein endothelial cells (HUVEC) plated on the Matrigel matrix substratum, we report here that TFFs are proangiogenic factors. Angiogenic activity of TFFs is comparable to that induced by vascular endothelial growth factor, leptin, and transforming growth factor-alpha. Stimulation of angiogenesis by pS2 in the CAM assay is blocked by pharmacological inhibitors of cyclooxygenase COX-2 (NS-398) and epidermal growth factor receptor (EGF-R) tyrosine kinase (ZD1839), but is independent of KDR/Flk-1 and thromboxane A2 receptors. In contrast, the morphogenic switch induced by pS2 in HUVEC cells could be inhibited by the specific KDR heptapeptide antagonist ATWLPPR and by inhibitors of COX-2 and EGF-R signaling. These results implicate TFFs in the formation of new blood vessels during normal and pathophysiological processes linked to wound healing, inflammation, and cancer progression in the digestive mucosa and other human solid tumors associated with aberrant expression of TFFs.