Melanocyte transformation associated with substrate adhesion impediment
Melanocyte transformation associated with substrate adhesion impediment
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DOI：
10.1593/neo.05781
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发表时间：
2006-03-01
期刊：
影响因子：
4.8
通讯作者：
Jasiulionis, Miriam G.
中科院分区：
文献类型：
--
作者：
Oba-Shinjo, Sueli M.;Correa, Mariangela;Jasiulionis, Miriam G.
恶性转化的实验模型采用化学和物理致癌物或遗传操作来研究肿瘤的进展。在这项工作中，不同的黑色素瘤细胞系建立后，提交一个非致瘤性黑色素细胞谱系（melan-a）的顺序周期的强制锚定障碍。绝大多数这些细胞进行失巢凋亡时，保持在悬浮液中。在一个去粘附周期后，在少数存活细胞中表型改变是明显的，这些细胞在每个粘附阻碍步骤后变得更多并显示出进行性改变。整合素的细胞表面表达未检测到显著差异，但在转化细胞系中观察到β（1）链的明显电泳迁移位移，与改变的糖基化模式一致。同时，三触角和四触角N-聚糖的逐渐富集是明显的，表明N-乙酰葡糖胺基转移酶V活性增加。在转化过程中检测到蛋白聚糖糖基化模式和核心蛋白表达的改变。总之，该模型证实了粘附状态作为转化过程中的促进剂的作用，并表明细胞粘附紊乱可能作为致癌刺激，至少对于非致瘤性永生化黑素细胞谱系。这些研究结果有有趣的影响，在体内致癌，这表明锚定独立性可能先于，并有助于，肿瘤转化。
Exclude experimental models of malignant transformationemploy chemical and physical carcinogens or genetic manipulations to study tumor progression. In this work, different melanoma cell lines were established after submitting a nontumorigenic melanocyte lineage (melan-a) to sequential cycles of forced anchorage impediment. The great majority of these cells underwent anoikis when maintained in suspension. After one deadhesion cycle, phenotypic alterations were noticeable in the few surviving cells, which became more numerous and showed progressive alterations after each adhesion impediment step. No significant differences in cell surface expression of integrins were detected, but a clear electrophoretic migration shift, compatible with an altered glycosylation pattern, was observed for beta(1) chain in transformed cell lines. In parallel, a progressive enrichment of tri- and tetra-antennary N-glycans was apparent, suggesting increased N-acetylglucosaminyl-transferase V activity. Alterations both in proteoglycan glycosylation pattern and core protein expression were detected during the transformation process. In conclusion, this model corroborates the role of adhesion state as a promoting agent in transformation process and demonstrates that cell adhesion disturbances may act as carcinogenic stimuli, at least for a nontumorigenic immortalized melanocyte lineage. These findings have intriguing implications for in vivo carcinogenesis, suggesting that anchorage independence may precede, and contribute to, neoplastic conversion.