Melanoma heterogeneity: differential, invasive, metastatic properties and profiles of cathepsin B, D and L activities in subclones of the B16F10-NEX22 cell line
Melanoma heterogeneity: differential, invasive, metastatic properties and profiles of cathepsin B, D and L activities in subclones of the B16F10-NEX22 cell line
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DOI：
10.1097/00008390-200410000-00002
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发表时间：
2004-10-01
影响因子：
2.2
通讯作者：
Travassos, LR
中科院分区：
文献类型：
--
作者：
Freitas, ZFO;Rodrigues, EG;Travassos, LR
肿瘤细胞系和体内生长的肿瘤是异质性的，由不同的细胞克隆组成。为了了解为什么有些细胞主要侵袭组织，而另一些细胞更容易转移，从已建立的B16F10-Nex2细胞系中分离出几个克隆，并将每个克隆中的105个活细胞静脉注射到C57B1/6和Balb/c小鼠体内。两个细胞克隆(Nex2B和Nex2D)显示出不同的转移能力。静脉注射后，克隆2D而不是克隆2B在两只小鼠的肺内定植。令人惊讶的是，在皮下植入后，克隆2B比2D生长得更快，显著降低了注射的小鼠的存活率。显然，在同一肿瘤细胞系的克隆中观察到了皮下生长和转移能力之间的分离。克隆Nex2B持续释放包括组织蛋白酶B在内的蛋白分解活性，并表现出比克隆Nex2D更强的侵袭Matrigel的能力。克隆Nex2D在细胞内积累了组织蛋白酶B、D和L，并在体外释放了中等的蛋白水解酶活性，但随着孵育时间的延长，活性受到抑制。皮下注射E-处理的Nex2B细胞显示出显着的延缓肿瘤发展和提高挑战动物存活率的作用。用克氏锥虫半胱氨酸蛋白酶抑制剂Chagin处理2B克隆也得到了类似的结果，即使在2um。克隆Nex2D对半胱氨酸蛋白酶抑制剂在体内的肿瘤发展不敏感。我们的结果表明，在肿瘤细胞群体中，细胞分裂为转移性和非转移性亚型，组织蛋白的释放或积累可能是这些细胞的一个不同特征。(C)2004年，里平科特·威廉姆斯·威尔金斯。
Tumour cell lines and in vivo growing tumours are heterogeneous, comprising different cell clones. To understand why some cells primarily invade a tissue, while others are more apt to metastasize, several clones from the established B16F10-Nex2 cell line were isolated and 105 viable cells of each clone were injected intravenously into C57B1/6 and Balb/c mice. Two cell clones (Nex2B and Nex2D) showed contrasting metastatic abilities. Clone 2D rather than clone 2B colonized the lungs of both mice after intravenous injection. Surprisingly, clone 2B grew more rapidly than 2D after subcutaneous implantation, significantly reducing the survival of injected mice. Clearly, dissociation between subcutaneous growth and metastatic ability was observed in clones from the same tumour cell lineage. Clone Nex2B continuously released proteolytic activity, including cathepsin B, and showed a greater capacity to invade Matrigel than clone Nex2D. Clone Nex2D accumulated cathepsins B, D and L intracellularly and released a moderate proteolytic activity in vitro that was inhibited with the time of incubation. E-64-treated Nex2B cells injected subcutaneously showed a significant delay in tumour development and increased survival of challenged animals. A similar result was obtained on treatment of clone 2B with chagasin, a cysteine proteinase inhibitor from Trypanosoma cruzi, even at 2 muM. Clone Nex2D was less sensitive to pretreatment with inhibitors of cysteine proteases for tumour development in vivo. Our results suggest that, in a tumour cell population, cells dissociate into metastatic and non-metastatic subtypes, and that release or accumulation of cathepsins can be a differential trait of these cells. (C) 2004 Lippincott Williams Wilkins.