IDENTIFICATION OF AN AMINO-ACID-SEQUENCE FROM THE LAMININ-A CHAIN THAT STIMULATES METASTASIS AND COLLAGENASE-IV PRODUCTION
IDENTIFICATION OF AN AMINO-ACID-SEQUENCE FROM THE LAMININ-A CHAIN THAT STIMULATES METASTASIS AND COLLAGENASE-IV PRODUCTION
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DOI：
10.1073/pnas.87.6.2279
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发表时间：
1990-03-01
影响因子：
11.1
通讯作者：
KLEINMAN, HK
中科院分区：
文献类型：
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作者：
KANEMOTO, T;REICH, R;KLEINMAN, HK
肿瘤细胞在转移过程中通过基底膜附着、降解和迁移。层粘连蛋白是基底膜上的一种主要糖蛋白，通过刺激细胞的附着和迁移以及胶原酶IV的分泌来促进肿瘤细胞的转移活性。我们已经从层粘连蛋白a链序列中发现了一个由19个氨基酸组成的合成肽（cys - ser - arg - ala - arg - lys - gln - ala - ala - ile - lys - val - ala - val - ser - ala - asp - arg），该肽增加了小鼠黑色素瘤细胞肺转移的实验。无论是静脉注射还是腹腔注射，这种肽都是有活性的。这种肽增加了胶原酶IV的活性，胶原酶IV是基底膜分解的关键酶，其程度与层粘连蛋白相同。该肽代表层粘连蛋白上促进转移表型的活性位点，并为研究恶性活动的调节提供了一个探针。
Tumor cells attach, degrade, and migrate through basement membranes as they metastasize. Laminin, a major glycoprotein of basement membranes, promotes the metastatic activity of tumor cells by stimulating the attachment and migration of the cells and their secretion of collagenase IV. We have identified a synthetic peptide of 19 amino acids (Cys-Ser-Arg-Ala-Arg-Lys-Gln-Ala-Ala-Ser-Ile-Lys-Val-Ala-Val-Ser-Ala-Asp-Arg) from the sequence of the A chain of laminin that increases experimental metastases of the lungs by murine melanoma cells. The peptide is active when injected either intravenously or intraperitoneally. The peptide increased collagenase IV activity, a key enzyme in the breakdown of basement membranes, to the same extent as laminin. This peptide represents an active site on laminin for promotion of the metastatic phenotype and generates a probe for studying the regulation of malignant activities.