Kuratomi Y, Nomizu M, Tanaka K, Ponce M L, Komiyama S, Kleinman H K, Yamada Y
Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, MD 20892, USA.
Br J Cancer. 2002 Apr 8;86(7):1169-73. doi: 10.1038/sj.bjc.6600187.
Laminin-1, a heterotrimer of alpha 1, beta 1, and gamma 1 chains specific to basement membrane, promotes cell adhesion and migration, proteinase secretion and metastases of tumour cells. Several active sites on the alpha 1 chain have been found to promote B16-F10 melanoma lung colonisation and here we have determined whether additional tumour promoting sites exist on the beta 1 and gamma 1 chains. Recently, we have identified novel cell adhesive peptides derived from laminin beta 1 and gamma 1 chains by systematic screening of synthetic peptides. Nine beta 1 peptides and seven gamma 1 peptides active for cell adhesion were tested for their effects on experimental pulmonary metastases of B16-F10 mouse melanoma cells in vivo. The most active adhesive peptide derived from the gamma 1 chain globular domain, C-16 (KAFDITYVRLKF), significantly enhanced pulmonary metastases of B16-F10 cells, whereas no other peptides showed enhancement. C-16 also stimulated migration of B16-F10 cells in the Boyden chamber assay in vitro. Furthermore, C-16 significantly induced the production of MMP-9 from B16-F10 cells. These results suggest that this specific laminin gamma 1 chain peptide has a metastasis-promoting activity and might be a new molecular target of anti-cancer treatment.
层粘连蛋白-1是一种基底膜特有的由α1、β1和γ1链组成的异源三聚体,可促进细胞黏附与迁移、蛋白酶分泌以及肿瘤细胞转移。已发现α1链上的几个活性位点可促进B16-F10黑色素瘤在肺部的定植,在此我们确定β1链和γ1链上是否存在其他促肿瘤位点。最近,我们通过对合成肽进行系统筛选,鉴定出了源自层粘连蛋白β1链和γ1链的新型细胞黏附肽。对9种具有细胞黏附活性的β1肽和7种γ1肽进行了测试,以观察它们对B16-F10小鼠黑色素瘤细胞体内实验性肺转移的影响。源自γ1链球状结构域的活性最强的黏附肽C-16(KAFDITYVRLKF)显著增强了B16-F10细胞的肺转移,而其他肽均未表现出增强作用。在体外Boyden小室实验中,C-16还刺激了B16-F10细胞的迁移。此外,C-16显著诱导B16-F10细胞产生MMP-9。这些结果表明,这种特定的层粘连蛋白γ1链肽具有促转移活性,可能是抗癌治疗的新分子靶点。