BIOCHEMICAL REGULATION OF ADENYLATE-CYCLASE IN MURINE MELANOMA CLONES WITH DIFFERENT METASTATIC PROPERTIES
BIOCHEMICAL REGULATION OF ADENYLATE-CYCLASE IN MURINE MELANOMA CLONES WITH DIFFERENT METASTATIC PROPERTIES
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DOI：
10.1002/ijc.2910370512
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发表时间：
1986-05-15
影响因子：
6.4
通讯作者：
POSTE, G
中科院分区：
文献类型：
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作者：
SHEPPARD, JR;LESTER, B;POSTE, G
在完整细胞和分离的膜制剂中，研究了不同转移能力的小鼠黑色素瘤细胞克隆中腺苷酸环化酶的调节。对一些B16黑色素瘤克隆的完整细胞反应的分析表明，用黑素细胞刺激素(MSH)或二萜Forsklin处理后，强转移克隆的细胞内环磷酸腺苷(CAMP)积累明显高于弱转移克隆。相反，在同一组克隆的分离膜中，Forskolin而不是MSH的激活程度与转移能力相关。氟化钠和5‘-鸟苷-β-伽马亚胺二磷酸[GPP(NH)p]也能刺激离体膜上的腺苷环化酶，但激活的程度与供体细胞的转移行为无关。Forskolin和GPP(NH)p的组合被证明是识别单个B16黑色素瘤克隆转移能力差异的一个敏感的前瞻性指标。转移能力较强的B16克隆细胞膜片中的腺苷酸环化酶表现出协同激活作用，而转移能力较弱的克隆细胞对腺苷环化酶的刺激作用较弱。为了测试这些发现的普遍性，对B16-BL6黑色素瘤细胞和K1735细胞进行了类似的研究，B16-BL6黑色素瘤细胞是B16黑色素瘤的高侵袭性亚系，K1735是紫外线诱导的小鼠黑色素瘤，发生在不同的小鼠品系(C3H)中。与B16-B16黑色素瘤的高转移潜能一致，来自B16-B16黑色素瘤的克隆细胞表现出激素刺激的腺苷环化酶水平升高，从而证实了该肿瘤系统的激素反应性与转移能力之间的密切联系。相反，K1735黑色素瘤细胞克隆在腺苷环化酶活性和转移性能方面表现出显著的克隆间差异，但没有发现这两个性状之间的一致关系。腺苷环化酶调节和/或内在催化能力的差异可能至少部分解释了在具有不同转移特性的B16克隆之间观察到的激素反应的差异，并提示B16黑色素瘤实验转移潜能的表达可能需要cAMP依赖的分子过程。未能在K1735黑色素瘤细胞中检测到cAMP代谢和转移性能之间的类似关联，表明这一分子过程不是转移性肿瘤细胞的恒定特征，并表明来自共同细胞谱系的肿瘤细胞的转移能力涉及不同的表型异常。
The regulation of adenylate cyclase in murine melanoma tumor cell clones with different metastatic capacities has been studied in intact cells and isolated membrane preparations. Analysis of the responses of intact cells from a number of B16 melanoma clones revealed that treatment with melanocyte-stimulating hormone (MSH) or the diterpene, forskolin, produced significantly greater accumulation of intracellular cyclic adenosine 3'',5'' monophosphate (cAMP) in strongly metastatic clones than in weakly metastatic tumor cell clones. In contrast, in isolated membranes from the same panel of clones, the extent of activation by forskolin but not by MSH correlated with metastatic capacity. Sodium fluoride and 5''-guanyl-.beta.-.gamma.-imidodiphosphate [Gpp(NH)p] also stimulated adenylate cyclase in isolated membranes but the extent of activation did not correlate with the metastatic behavior of the donor cells. A combination of forskolin and Gpp(NH)p proved to be a sensitive prospective indicator for identifying differences in the metastatic capabilities of individual B16 melanoma clones. Adenylate cyclase in membrane preparations from strongly metastatic B16 clones displayed synergistic activation but stimulation of the enzyme from weakly metastatic clones was less then additive. To test the generality of these findings, similar investigations were performed on B16-BL6 melanoma cells, a highly invasive subline of the B16 melanoma, and the K1735, an ultraviolet-light-induced murine melanoma arising in a different mouse strain (C3H). Consistent with their high metastatic potential, clones derived from the B16-B16 melanoma displayed elevated levels of hormonally-stimulated adenylate cyclase, thereby confirming, for this tumor system, a close association between hormonal responsiveness and metastatic capacity. In contrast, K1735 melanoma cell clones exhibited significant interclonal variation in adenylate cyclase activity and metastatic performance, but no consistent relationship between the two traits was detected. Differences in the regulation and/or the intrinsic catalytic capacity of adenylate cyclase may account, at least in part, for the variation in hormonal responsiveness observed among B16 clones with distinct metastatic properties and suggest that cAMP-dependent molecular processes may be required for the expression of B16 melanoma experimental metastatic potential. The failure to detect a similar association between cAMP metabolism and metastatic performance in the K1735 melanoma cells indicates that this molecular process is not an invariant feature of metastatic tumor cells and suggests that metastatic competence in tumor cells arising from a common cell lineage involves diverse phenotypic aberrations.