Inhibition of metastatic cell colonization in murine lungs and tumor‐induced morbidity by non‐peptidic Arg‐Gly‐Asp mimetics
Inhibition of metastatic cell colonization in murine lungs and tumor‐induced morbidity by non‐peptidic Arg‐Gly‐Asp mimetics
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非肽 Arg-Gly-Asp 模拟物抑制小鼠肺部转移细胞定植和肿瘤诱发的发病率
DOI：
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发表时间：
1993
影响因子：
6.4
通讯作者：
O. Lider
中科院分区：
文献类型：
--
作者：
I. Hardan;L. Weiss;R. Hershkoviz;N. Greenspoon;R. Alon;L. Cahalon;S. Reich;S. Slavin;O. Lider
肿瘤细胞的扩散和定植需要它们通过血管迁移到转移部位。为了穿透血管壁，细胞（包括恶性细胞）必须识别并与内皮下细胞外基质（ECM）及其糖蛋白结合。ECM-糖蛋白（如纤连蛋白（FN）和玻连蛋白（VN））的识别由各种细胞类型（包括血小板、白细胞和肿瘤细胞）上表达的整联蛋白受体介导。含有Arg-Gly-Asp（RGD）的肽是ECM的主要粘附配体，存在于各种血浆和基质糖蛋白中，如FN和VN。RGD的非肽模拟物由Asp和Arg的羧酸盐和胍基组成，被线性原子间隔区分开，对α 11 b-β3整联蛋白表达高亲和力并抑制血小板聚集。在此，检查了RGD模拟物抑制肿瘤细胞和RGD之间的粘附相互作用以及体内肿瘤进展的能力。含有RGD的肽和RGD模拟物，化合物SF-6，5，而不是Arg-Gly-Glu（RGE）肽或相应的模拟物，特异性地抑制B16-F10黑色素瘤细胞与固定的VN和FN的粘附。在转移的实验和自发模型中，小鼠每日体内给予SF-6，5可抑制B16-F10集落的形成。此外，SF-6，5可以预防肺部肿瘤细胞大量定植引起的小鼠死亡。含RGD的肽对肿瘤转移形成的治疗效果是边缘性的，可能是由于使用的量少，以及其对原位蛋白水解的敏感性。因此，小粘附表位的非肽模拟物可以提供一种新的治疗工具，以预防涉及整合非依赖性细胞-细胞和细胞-ECM相互作用的不良病理事件。
The spreading and colonization of tumor cells require their migration to metastatic sites via blood vessels. To penetrate blood‐vessel walls, cells, including malignant ones, must recognize and associate with the sub‐endothelium extracellular matrix (ECM) and its glycoproteins. Recognition of ECM‐glycoproteins, such as fibronectin (FN) and vitronectin (VN), is mediated by integrin receptors expressed on various cell types, including platelets, leukocytes and tumor cells. The Arg‐Gly‐Asp (RGD)‐containing peptide, a major adhesive ligand of ECM, is present in various plasma and matrix glycoproteins, such as FN and VN. Non‐peptidic mimetics of RGD, consisting of carboxylate and guanidinium groups of Asp and Arg divided by a linear atom spacer, express a high affinity for the α11b ‐β3 integrin and inhibit platelet aggregation. Herein, the ability of RGD mimetics to inhibit adhesive interactions between tumor cells and RGD, and tumor progression in vivo, was examined. RGD‐containing peptides and the RGD mimetic, compound SF‐6,5, but not the Arg‐Gly‐Glu (RGE) peptide or the corresponding mimetic, specifically inhibited B16‐F10 melanoma cell adhesion to immobilized VN and FN. Daily administration in vivo of SF‐6,5 to mice inhibited the formation of B16‐F10 colonies in experimental and spontaneous models of metastases. Moreover, SF‐6,5 could prevent mouse death caused by massive colonization of tumor cells in the lungs. The therapeutic effect of RGD‐containing peptides on tumor metastasis formation was marginal, probably due to the small amounts used, and its susceptibility to proteolysis in situ. Thus, non‐peptidic mimetics of small adhesive epitopes may provide a novel therapeutic tool to prevent an adverse pathological event involving integrindependent cell‐cell and cell‐ECM interactions.
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影响因子：
11.2
作者：
K. Yamada;D. Kennedy;S. Yamada;H. Gralnick;Wen‐Tien Chen;S. K. Akiyama
通讯作者：
K. Yamada;D. Kennedy;S. Yamada;H. Gralnick;Wen‐Tien Chen;S. K. Akiyama
DOI：
10.1093/jnci/80.18.1461
发表时间：
1988-11
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
K. Ugen;M. Mahalingam;P. Klein;K. Kao
通讯作者：
K. Ugen;M. Mahalingam;P. Klein;K. Kao
albolabrin（一种从 Trimeresurus albolabris 毒液中分离出的含有 RGD 的肽）对小鼠黑色素瘤细胞基质粘附和实验性转移的抑制作用。
影响因子：
3.7
作者：
Soszka,T;Knudsen,KA;Beviglia,L;Rossi,C;Poggi,A;Niewiarowski,S
通讯作者：
Niewiarowski,S
影响因子：
13.8
作者：
DSOUZA, SE;GINSBERG, MH;PLOW, EF
通讯作者：
PLOW, EF
影响因子：
15.9
作者：
NIERODZIK, ML;PLOTKIN, A;KARPATKIN, S
通讯作者：
KARPATKIN, S