Andalib A R, Lawry J, Ali S A, Murray A K, Sisley K, Silcocks P, Herlyn M, Rees R C
Institute for Cancer Studies, Sheffield University Medical School, UK.
Melanoma Res. 1997 Feb;7(1):32-42. doi: 10.1097/00008390-199702000-00006.
The constitutive and cytokine-mediated expression of MHC class I and II antigens and intercellular adhesion molecule-1 (ICAM-1) was evaluated on eight human melanoma cell lines derived from primary and metastatic malignancies from patients (WM human melanoma series) including three pairs of related cell lines derived from the same individual. The cytokines IL-1 beta, IL-4, IL-6, TNF alpha, TGF beta 2, IFN gamma and IFN alpha were assessed for their ability to modulate the expression of cell surface antigens. MHC class I and class II antigen expression was unregulated by IFN gamma, IFN alpha and/or TNF alpha in cell lines established from primary melanoma. In contrast the cell lines derived from metastatic deposits did not show an increase in expression of MHC antigens in response to these cytokines. Both primary and metastatic WM cell lines were shown to be resistant to spontaneous natural killer cell (NK) activity, but susceptible to effector lymphocytes mediating lymphotine activated killer (LAK) cytotoxicity as a result of activation by IL-2. Although the constitutive and cytokine-induced level of expression of ICAM-1 and MHC antigens varied between paired primary and metastatic cell lines, this did not correlate with susceptibility of the cell line target to NK or LAK cytotoxicity. Whereas the IFNs, TNF alpha, TGF beta 2 and IL-1 beta differentially modulated the expression of ICAM-1 and MHC class I, treatment with IFNs (but not IL-1 beta, TNF alpha or TGF beta 2) resulted in a significant reduction in the sensitivity of the melanoma cells to NK and LAK cytotoxicity. Constitutive ICAM-1 expression was positively correlated with the ability of WM cell lines to colonise the lungs of SCID mice upon i.v. injection. The acquisition of cytokine resistance and inability to demonstrate enhanced cell surface expression may represent an important feature associated with the development of the metastatic phenotype.
对来自患者原发性和转移性恶性肿瘤的8个人类黑色素瘤细胞系（WM人类黑色素瘤系列），包括来自同一个体的三对相关细胞系，评估了主要组织相容性复合体（MHC）I类和II类抗原以及细胞间黏附分子-1（ICAM-1）的组成性和细胞因子介导的表达。评估了细胞因子白细胞介素-1β（IL-1β）、白细胞介素-4（IL-4）、白细胞介素-6（IL-6）、肿瘤坏死因子α（TNFα）、转化生长因子β2（TGFβ2）、干扰素γ（IFNγ）和干扰素α（IFNα）调节细胞表面抗原表达的能力。在从原发性黑色素瘤建立的细胞系中，MHC I类和II类抗原表达不受IFNγ、IFNα和/或TNFα的调节。相反，来自转移灶的细胞系对这些细胞因子没有表现出MHC抗原表达增加。原发性和转移性WM细胞系均显示对自发自然杀伤细胞（NK）活性具有抗性，但由于IL-2激活，对介导淋巴因子激活杀伤细胞（LAK）细胞毒性的效应淋巴细胞敏感。尽管配对的原发性和转移性细胞系之间ICAM-1和MHC抗原的组成性和细胞因子诱导表达水平有所不同，但这与细胞系靶标对NK或LAK细胞毒性的敏感性无关。虽然IFN、TNFα、TGFβ2和IL-1β对ICAM-1和MHC I类的表达有不同调节作用，但用IFN（而非IL-1β、TNFα或TGFβ2）处理会导致黑色素瘤细胞对NK和LAK细胞毒性的敏感性显著降低。组成性ICAM-1表达与WM细胞系经静脉注射后在严重联合免疫缺陷（SCID）小鼠肺部定植的能力呈正相关。获得细胞因子抗性以及无法表现出增强的细胞表面表达可能代表与转移表型发展相关的一个重要特征。
