EXPERIMENTAL METASTASIS CORRELATES WITH CYCLIC-AMP ACCUMULATION IN B-16 MELANOMA CLONES
EXPERIMENTAL METASTASIS CORRELATES WITH CYCLIC-AMP ACCUMULATION IN B-16 MELANOMA CLONES
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DOI：
10.1038/308544a0
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发表时间：
1984-01-01
期刊：
影响因子：
64.8
通讯作者：
POSTE, G
中科院分区：
文献类型：
--
作者：
SHEPPARD, JR;KOESTLER, TP;POSTE, G
转移是一个复杂的过程，来自原发肿瘤生长的肿瘤细胞扩散到全身，并在远处器官建立继发肿瘤灶。与转移表型表达相关或必需的生化特征尚未确定1，2。在检测黑素细胞刺激素(MSH)和二萜Forsklin对B16小鼠黑色素瘤腺苷环化酶刺激的过程中，我们注意到从共同亲本细胞群体中分离的肿瘤细胞克隆3-5对这些激动剂的反应有很大差异。我们在此报道，MSH或Forsklin诱导的cAMP积聚与B16黑色素瘤克隆静脉注射时形成肺肿瘤克隆的能力呈强烈的正相关。转化为同基因小鼠(“实验性转移”)。在循环AMP代谢的平行体外分析和使用复制细胞制备的实验性转移的活体分析中，高转移肿瘤细胞克隆始终显示，当暴露于MSH或Forsklin时，细胞循环AMP增加了30倍以上。相比之下，转移能力有限的克隆对相同的激动剂的反应只有两到三倍的细胞周期AMP增加。这些数据表明，循环AMP代谢与生化途径有关，这些途径是B16黑色素瘤实验性转移形成的原因。
Metastasis is a complex process whereby tumour cells from a primary neoplastic growth disseminate throughout the body and establish secondary tumour foci in distant organs. Biochemical traits associated with, or essential for, the expression of the metastatic phenotype have not yet been identified1,2. In the course of examining stimulation of the B16 murine melanoma adenylate cyclase by melanocyte-stimulating hormone (MSH) and by the diterpene forskolin, we noted that tumour cell clones3–5isolated from common parent cell populations differed widely in their responses to these agonists. We report here that the accumulation of cyclic AMP induced by MSH or forskolin shows a strong positive correlation with the ability of B16 melanoma clones to form pulmonary tumour colonies when injected intravenously (i.v.) into syngeneic mice (‘experimental metastasis’). In parallelin vitroanalyses of cyclic AMP metabolism andin vivoassays of experimental metastasis using replicate cell preparations, highly metastatic tumour cell clones consistently show greater than a 30-fold increase in cellular cyclic AMP when exposed to MSH or forskolin. By contrast, clones with limited metastatic abilities respond to the same agonists with only a two- to threefold increase in cellular cyclic AMP. These data suggest that cyclic AMP metabolism is linked with biochemical pathways that are responsible for the formation of experimental metastasis by the B16 melanoma.