Laminin-α1-chain sequence Leu-Gln-Val-Gln-Leu-Ser-Ile-Arg (LQVQLSIR) enhances murine melanoma cell metastases
Laminin-α1-chain sequence Leu-Gln-Val-Gln-Leu-Ser-Ile-Arg (LQVQLSIR) enhances murine melanoma cell metastases
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DOI：
10.1002/(sici)1097-0215(19980812)77:4
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发表时间：
1998-08-12
影响因子：
6.4
通讯作者：
Yamada, Y
中科院分区：
文献类型：
--
作者：
Kim, WH;Nomizu, M;Yamada, Y
我们早期筛选重叠的合成肽从层粘连蛋白α 1链的球状结构域，以确定细胞附着的活性位点。我们在这里报告的活性细胞粘附肽之一，AG-73（Arg-Lys-Arg-Leu-Gln-Val-Gln-Leu-Ser-Ile-Arg-Thr; RKRLQVQLSIRT）导致B16-F10小鼠黑色素瘤细胞转移到肝脏，一个网站，通常不会由这些细胞殖民。在免疫缺陷的米色/裸/xid和C57 BI/6小鼠中观察到肝转移和肺定殖的增加。无论肿瘤细胞或肽注射时间如何，静脉内和腹膜内肽注射均观察到这种转移活性。在体外，AG-73肽增强肿瘤细胞粘附、迁移、侵袭和明胶酶产生，并阻断层粘连蛋白-1介导的细胞迁移。发现AG-73显著抑制细胞粘附于含有AG-73序列的蛋白水解层粘连蛋白-1片段E3。细胞附着到AG-73、E3片段和层粘连蛋白-1涉及阳离子依赖性受体。我们报道了一种层粘连蛋白肽具有新的和意想不到的活性，能引起B16 F10黑色素瘤细胞（一种肺选择性细胞系）转移到肝脏。AG-73的最小活性序列LQVQLSIR可能是层粘连蛋白-1最重要的生物活性位点之一，尤其是在促进恶性表型方面。这种肽激活恶性表型为理解转移机制提供了一个重要的新模型。Int. i. Cancer 77：632-639，1998. (C)1998 Wiley-Liss，Inc.匕首。
We earlier screened overlapping synthetic peptides from the globular domain of the laminin alpha 1 chain to identify active sites for cell attachment. We report here that one of the active cell-adhesion peptides, AG-73 (Arg-Lys-Arg-Leu-Gln-Val-Gln-Leu-Ser-Ile-Arg-Thr; RKRLQVQLSIRT) causes B16-F10 murine melanoma cells to metastasize to the liver, a site not normally colonized by these cells. Increases in liver metastases and in lung colonization are observed in immune-deficient beige/nude/xid and in C57BI/6 mice with this peptide. This metastatic activity was observed with i.v. and with i.p. peptide injections, regardless of tumor cell or of peptide-injection times. In vitro, the AG-73 peptide enhances tumor cell adhesion, migration, invasion, and gelatinase production, and blocks laminin-1-mediated cell migration. AG-73 was found to significantly inhibit cell adhesion to a proteolytic laminin-1 fragment, E3, containing the AG-73 sequence. Cell attachment to AG-73, the E3 fragment, and laminin-1 involved cation-dependent receptors. We report that a laminin peptide has the novel and unexpected activity of causing B16F10 melanoma cells, a lung selected cell line, to metastasize to the liver. The minimal active sequence of AG-73, LQVQLSIR, could be one of the most important biologically active sites of laminin-1, especially in promotion of the malignant phenotype. Activation of the malignant phenotype by this peptide provides a significant new model for understanding metastatic mechanisms. Int. i. Cancer 77:632-639, 1998. (C) 1998 Wiley-Liss, Inc.dagger.