Inhibition of murine melanoma cell-matrix adhesion and experimental metastasis by albolabrin, an RGD-containing peptide isolated from the venom of Trimeresurus albolabris.

Inhibition of murine melanoma cell-matrix adhesion and experimental metastasis by albolabrin, an RGD-containing peptide isolated from the venom of Trimeresurus albolabris.
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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。

DOI:
10.1016/0014-4827(91)90449-5
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发表时间:
1991
影响因子:
3.7
通讯作者:
Niewiarowski,S
Niewiarowski,S
中科院分区:
医学3区
文献类型:
--
作者:
Soszka,T;Knudsen,KA;Beviglia,L;Rossi,C;Poggi,A;Niewiarowski,S

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白唇青蛇毒蛋白(Albolabrin)是从白唇竹叶青蛇(Trimeresurus albolabris)毒液中分离出的一种富含7.5kDa半胱氨酸的蛋白质,其含有在许多细胞粘附促进细胞外基质蛋白(如纤连蛋白和层粘连蛋白)中发现的精氨酸-甘氨酸-天冬氨酸(RGD)细胞识别序列。Albolabrin属于含RGD的肽家族,称为去整合素,最近从各种毒蛇的毒液中分离出来,并发现是血小板聚集和细胞基质粘附的有效抑制剂。在这里,我们报告,albolabrin抑制附着的B16-F10小鼠黑色素瘤细胞的纤维连接蛋白或层粘连蛋白吸收塑料。当被固定在塑料上时,白白蛋白促进B16-F10黑色素瘤细胞附着;这被RGD-丝氨酸(RGDS)或整联蛋白抗体抑制,表明白蛋白通过其RGD氨基酸序列与黑色素瘤细胞表面表达的整联蛋白受体结合。在体外实验转移系统中,浓度为300-600 nMin的白藜芦醇抑制了尾静脉注射的小鼠黑素瘤细胞对C57 BL/6小鼠肺的定殖,并且在该测定中比RGDS的活性高至少2000倍。我们提出白纹伊蚊素通过抑制黑色素瘤细胞与小鼠肺细胞外基质中含RGD成分的整合素介导的粘附来抑制肿瘤细胞转移。
Albolabrin, a 7.5-kDa cysteine-rich protein isolated from the venom ofTrimeresurus albolabris, contains the arginine-glycine-aspartic acid (RGD) cell recognition sequence found in many cell adhesion-promoting extracellular matrix proteins, such as flbronectin and laminin. Albolabrin belongs to a family of RGD-containing peptides, termed disintegrins, recently isolated from the venom of various vipers and discovered to be potent inhibitors of both platelet aggregation and cell-substratum adhesion. Here we report that albolabrin inhibited the attachment of B16-F10 mouse melanoma cells to either flbronectin or laminin absorbed on plastic. When immobilized on plastic, albolabrin promoted B16-F10 melanoma cell attachment; this was inhibited by either RGD-serine (RGDS) or antibodies to integrins, suggesting that albolabrin binds via its RGD amino sequence to integrin receptors expressed on the melanoma cell surface. In anin vivoexperimental metastasis system, albolabrin at a concentration of 300–600 nMinhibited C57BL/6 mouse lung colonization by tail vein-injected mouse melanoma cells and was at least 2000 times more active than RGDS in this assay. We propose that albolabrin inhibits tumor cell metastasis by inhibiting integrin-mediated attachment of melanoma cells to RGD-containing components of the extracellular matrix in the mouse lung.