Giuffrè L, Schreyer M, Mach J P, Carrel S
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
Cancer. 1988 Mar 15;61(6):1132-41. doi: 10.1002/1097-0142(19880315)61:6<1132::aid-cncr2820610613>3.0.co;2-q.
Treating human melanoma lines with dibutyryl adenosine 3':5'-cyclic monophosphate (dbc AMP) resulted in morphologic changes associated with the altered expression of cell surface antigens. After treatment, cells developed long cellular projections characteristic of mature melanocytes and showed the presence of an increased number of Stage II premelanosomes. In addition, induction of melanin synthesis, detected as brown perinuclear pigmentation, was observed. The AMP further drastically reduced the growth rate of the five melanoma cell lines that were tested. The influence of dbc AMP was completely reversible 3 days after the agent was removed from the culture medium. The antigenic phenotype of the melanoma lines was compared before and after dbc AMP treatment. This was done with four monoclonal antibodies directed against major histocompatibility complex (MHC) Class I and II antigens and 11 monoclonal antibodies defining eight different melanoma-associated antigenic systems. Treatment with dbc AMP reduced the expression of human leukocyte antigen (HLA)-ABC antigens and beta-2-microglobulin in five of five melanoma lines. In the two HLA-DR-positive cell lines dbc AMP reduced the expression of this antigen in one line and enhanced it in the other. No induction of HLA-DR or HLA-DC antigens was observed in the Class II negative cell lines. Furthermore, dbc-AMP modulated the expression of the majority of the melanoma antigenic systems tested. The expression of a 90-kilodalton (KD) antigen, which has been found to be upregulated by interferon-gamma, was markedly decreased in all the five cell lines. A similar decrease in the expression of the high molecular weight proteoglycan-associated antigen (220-240 KD) was observed. The reduced expression of Class I and II MHC antigens as well as the altered expression of the melanoma-associated antigens studied were shown to be reversible after dbc AMP was removed. Our results collectively show that the monoclonal antibody-defined melanoma-associated molecules are linked to differentiation. They could provide useful tools for monitoring the maturation of melanomas in vivo induced by chemical agents or natural components favoring differentiation.
用二丁酰腺苷 3':5'-环磷酸（dbc AMP）处理人黑色素瘤细胞系，导致细胞形态发生改变，这与细胞表面抗原表达的改变有关。处理后，细胞形成了成熟黑素细胞特有的长细胞突起，并显示出II期前黑素小体数量增加。此外，观察到黑色素合成的诱导，表现为核周棕色色素沉着。AMP进一步显著降低了所测试的五种黑色素瘤细胞系的生长速率。从培养基中去除dbc AMP 3天后，其影响完全可逆。比较了dbc AMP处理前后黑色素瘤细胞系的抗原表型。使用针对主要组织相容性复合体（MHC）I类和II类抗原的四种单克隆抗体以及定义八个不同黑色素瘤相关抗原系统的11种单克隆抗体进行了此项研究。用dbc AMP处理使五种黑色素瘤细胞系中的五种细胞系中人白细胞抗原（HLA）-ABC抗原和β2-微球蛋白的表达降低。在两个HLA-DR阳性细胞系中，dbc AMP使一个细胞系中该抗原的表达降低，而在另一个细胞系中使其增强。在II类阴性细胞系中未观察到HLA-DR或HLA-DC抗原的诱导。此外，dbc-AMP调节了所测试的大多数黑色素瘤抗原系统的表达。在所有五个细胞系中，一种已被发现受干扰素-γ上调的90千道尔顿（KD）抗原的表达明显降低。观察到高分子量蛋白聚糖相关抗原（220 - 240 KD）的表达也有类似降低。去除dbc AMP后，I类和II类MHC抗原表达的降低以及所研究的黑色素瘤相关抗原表达的改变显示是可逆的。我们的结果共同表明，单克隆抗体定义的黑色素瘤相关分子与分化有关。它们可为监测体内由化学试剂或促进分化的天然成分诱导的黑色素瘤成熟提供有用工具。
