RGD peptides and monoclonal antibodies, antagonists of αv-integrin, enter the cells by independent endocytic pathways
RGD peptides and monoclonal antibodies, antagonists of αv-integrin, enter the cells by independent endocytic pathways
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DOI：
10.1038/labinvest.3780375
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发表时间：
2001-12-01
影响因子：
5
通讯作者：
Reina, M
中科院分区：
文献类型：
--
作者：
Castel, S;Pagan, R;Reina, M
含有精氨酸-甘氨酸-天冬氨酸基序（cRGD）的环状合成肽和针对单个整合素的单克隆抗体（mab）已被开发为治疗多种疾病的潜在治疗药物。我们发现靶向α (v) β(3)的cRGD肽在α (v)-整合素表达和非表达的黑色素瘤细胞中通过不依赖整合素的液相内吞途径被内化，该途径不改变细胞表面功能性整合素受体的数量。相反，指向α (v)的阻断单抗通过整合素依赖的内吞途径内化，从而减少细胞表面功能性整合素受体的数量。我们证明，用单抗预处理的黑色素瘤细胞不能读取底物，而用cRGD肽预处理的细胞保留了其读取能力。鉴于RGD肽的重要性日益增加，需要了解这些细胞机制以改善抗血管生成和抗炎药物的开发。
Cyclic synthetic peptides containing the arginine-glycine-aspartate motif (cRGD) and monoclonal antibodies (mAbs) targeted for individual integrins have been developed as potential therapeutic drugs for the treatment of several diseases. We showed that a cRGD peptide targeted for alpha (v)beta (3) was internalized in alpha (v)-integrin expressing and nonexpressing melanoma cells by an integrin independent fluid-phase endocytosis pathway that does not alter the number of functional integrin receptors at the cell surface. In contrast, a blocking mAb directed to alpha (v) was internalized by an integrin-dependent endocytosis pathway that reduced the number of functional integrin receptors at the cell surface. We prove that melanoma cells pretreated with the mAb do not readhere to the substrate, whereas cells pretreated with cRGD peptide retain their readhesion capacity. Given the growing importance of RGD peptides, knowledge of these cellular mechanisms is required to improve the development of antiangiogenic and anti-inflammatory drugs.