Synthetic peptides inhibit adhesion of human tumor cells to extracellular matrix proteins.
Synthetic peptides inhibit adhesion of human tumor cells to extracellular matrix proteins.
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发表时间：
2001-04
期刊：
影响因子：
11.2
通讯作者：
DeRoock Ib;M. Pennington;T. Sroka;Kit S. Lam;G. Bowden;E. L. Bair;A. Cress
中科院分区：
文献类型：
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作者：
DeRoock Ib;M. Pennington;T. Sroka;Kit S. Lam;G. Bowden;E. L. Bair;A. Cress
人类肿瘤细胞的进展和转移部分依赖于肿瘤细胞粘附细胞外基质（ECM）蛋白并在远处存活的能力。分析了六种新型含d-氨基酸肽对人前列腺肿瘤细胞的粘附能力，支持肿瘤细胞粘附，抑制肿瘤细胞对ECM蛋白或人真皮成纤维细胞的粘附能力。其中，两种称为RZ-3 （kmviywkag）和HYD-1 （kikmviswkg）的肽结合到肿瘤细胞表面，并与先前报道的AG-73 (RKRLQVQLSIRT) l -氨基酸肽相比，通过荧光激活细胞分选分析确定。一种被称为HYDS-1 （wiksmkivkg）的混乱肽衍生物没有活性。RZ-3、HYD-1和AG-73肽分别在5 μ g、10 μ g和50 μ g/孔时支持最大的癌细胞粘附。ECM蛋白纤维连接蛋白、层粘连蛋白1和胶原蛋白IV分别在1 μ g、10 μ g和50 μ g/孔时支持最大的细胞粘附。α 2-6和β 1整合素阻断抗体可抑制前列腺肿瘤细胞对固定化RZ-3和HYD-1肽的粘附。相反，肿瘤细胞对β -整合素特异性抗体的粘附被RZ-3和HYD-1阻断。上皮细胞与真皮成纤维细胞的粘附被HYDS-1抑制，而不受搅合肽HYDS-1的影响。EDTA不影响细胞对固定肽的粘附。可溶性RZ-3和HYD-1肽以时间和浓度依赖性的方式抑制肿瘤细胞对固定的四种ECM蛋白的粘附（1.0微克/孔）。RZ-3肽阻断纤维连接蛋白、层粘连蛋白1、层粘连蛋白5和胶原IV粘附的IC（50）分别为2.4、1.8、4.6和2.8 μ g/孔。HYD-1肽阻断纤维连接蛋白、层粘连蛋白1、层粘连蛋白5和胶原IV粘附的IC（50）分别为6.9 μ g、5.7 μ g、bbb10 μ g和6.2 μ g/孔。综上所述，这些结果表明RZ-3和HYD-1是具有生物活性的含d氨基酸肽，它们本身可以支持肿瘤细胞粘附，并可以抑制肿瘤细胞对固定化ECM蛋白或真皮成纤维细胞的粘附。
Human tumor cell progression and metastasis are partially dependent on the ability of a tumor cell to adhere to the proteins of the extracellular matrix (ECM) and survive at the distant location. Six novel D-amino acid-containing peptides were analyzed for their ability to adhere to human prostate tumor cells, support tumor cell adhesion, and inhibit tumor cell adhesion to ECM proteins or human dermal fibroblasts. Of these, two peptides called RZ-3 (kmviywkag) and HYD-1 (kikmviswkg) bound to tumor cell surfaces and compared favorably with the previously reported AG-73 (RKRLQVQLSIRT) L-amino acid peptide, as determined by fluorescence-activated cell sorting analysis. A scrambled peptide derivative of HYD-1, called HYDS-1 (wiksmkivkg), was not active. The RZ-3, HYD-1, and AG-73 peptides supported maximal cancer cell adhesion at 5 microg, 10 microg, and 50 microg/well, respectively. The ECM proteins fibronectin, laminin 1, and collagen IV supported maximal cell adhesion at 1 microg, >10 microg, and 50 microg/well, respectively. Prostate tumor cell adhesion to immobilized RZ-3 and HYD-1 peptides was inhibited by alpha2-6- and beta1-integrin-blocking antibodies. Conversely, tumor cell adhesion to a beta1-integrin-specific antibody was blocked by both RZ-3 and HYD-1. Epithelial cell adhesion to dermal fibroblasts was inhibited by HYD-1 and unaffected by the scrambled peptide, HYDS-1. Cell adhesion to immobilized peptides was unaffected by EDTA. The soluble RZ-3 and HYD-1 peptides inhibited tumor cell adhesion to each of the immobilized four ECM proteins (1.0 microg/well) in a time- and concentration-dependent manner. The IC(50) of the RZ-3 peptide for blocking adhesion to fibronectin, laminin 1, laminin 5, and collagen IV was 2.4 microg, 1.8 microg, 4.6 microg, and 2.8 microg/well, respectively. The IC(50) of the HYD-1 peptide for blocking adhesion to fibronectin, laminin 1, laminin 5, and collagen IV was 6.9 microg, 5.7 microg, >10 microg, and 6.2 microg/well, respectively. Taken together, these results indicate that RZ-3 and HYD-1 are biologically active D-amino acid-containing peptides that can themselves support tumor cell adhesion and can inhibit tumor cell adhesion to immobilized ECM proteins or dermal fibroblasts.