DIFFERENTIATION AND THE TUMORIGENIC AND METASTATIC PHENOTYPE OF MURINE MELANOMA-CELLS

DIFFERENTIATION AND THE TUMORIGENIC AND METASTATIC PHENOTYPE OF MURINE MELANOMA-CELLS
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DOI:
10.1002/ijc.2910450627
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发表时间:
1990-06-15
影响因子:
6.4
通讯作者:
HEARING, VJ
HEARING, VJ
中科院分区:
医学1区
文献类型:
--
作者:
KAMEYAMA, K;VIEIRA, WD;HEARING, VJ

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使用从 JB/MS 黑色素瘤产生的 B126 F10 鼠黑色素瘤细胞和亚系(表现出不同程度的黑色素生成),检查了分化、致瘤性和转移潜力之间的关系。还研究了专门刺激黑素细胞分化的黑素细胞刺激激素(MSH)的作用。所有测试的黑色素瘤系都能够生长为实验性肺转移瘤,但令人惊讶的是,未分化和无黑色素的 JB/MS-w 细胞未能生长为原发性皮下肿瘤。 JB/MS-w 细胞表面 MSH 受体很少,与其他细胞系不同,JB/MS-w 细胞对 MSH 的反应不会导致黑色素生成增加。尽管用 MSH 进行体外治疗并没有改变这些细胞系原发肿瘤的生长速率,但这种治疗减少了 B16 F10、JB/MS 细胞、JB/MS-bl 细胞和 JB/MS-w 细胞的肺转移瘤数量。相反,MSH 治疗显着增加了 JB/MS-p 细胞的肺转移率。检查表面黑色素瘤抗原的表达、尿激酶型纤溶酶原活性和对自然杀伤细胞的敏感性。 MSH 并未显着改变表面黑色素瘤抗原表达,但增加了 B16 F10、JB/MS 和 JB/MS-bl 细胞(拥有丰富表面 MSH 受体的细胞)的自然杀伤细胞敏感性。体外分化(色素沉着)和增殖之间存在负相关,色素较多的黑色素瘤细胞(B16 F10、JB/MS 和 JB/MS-bl)表达相对较低水平的 I 类 MHC、相对较高水平的 II 类 MHC 和最高的转移能力。这些结果表明,MSH 不仅具有调节黑素生成的能力,还具有调节对细胞转移生长至关重要的其他因素的能力。
Using B126 F10 murine melanoma cells and sublines generated from the JB/MS melanoma which exhibit various degrees of melanogenesis, the relationships among differentiation, tumorigenicity, and metastatic potential were examined. The effect of melanocyte-stimulating hormone (MSH), which specifically stimulates differentiation of melanocytes, was also studied. All melanoma lines tested were capable of growing as experimental pulmonary metastases but, surprising, the undifferentiated and amelanotic JB/MS-w cells failed to grow as primary subcutaneous tumors. JB/MS-w cells, which had few surfce MSH receptors, did not respond to MSH with an increase in melanin production, unlike the other cell lines. Although in vitro treatment with MSH did not change the rates of growth of primary tumors by these cell lines, such treatment decreased the number of pulmonary metastases from B16 F10, JB/MS cells, JB/MS-bl cells and JB/MS-w cells. Conversely, MSH treatment significantly increased the rates of pulmonary metastases from JB/MS-p cells. The expression of surface melanoma antigens, urokinase-type plasminogen activity and susceptibility to natural killer cells were examined. MSH did not significantly alter surface melanoma antigen expression, but increased the natural killer cell susceptibility of B16 F10, JB/MS and JB/MS-bl cells, cells which possess abundant surface MSH receptors. There was an inverse correlation between differentiation (pigmentation) and proliferation in vitro, and the more pigmented melanoma cells (B16 F10, JB/MS and JB/MS-bl) expressed relative lower levels of class-I MHC, relatively higher levels of class-II MHC and the highest metastatic capacity. These results demonstrate that MSH possesses the capacity to regulate not only melanogenesis, but also other factors critical to the metastatic growth of the cells.