Armstrong C A, Tara D C, Hart C E, Köck A, Luger T A, Ansel J C
Dermatology Service, Veterans Affairs Medical Center, Portland, Oregon 97207.
Exp Dermatol. 1992 Jul;1(1):37-45. doi: 10.1111/j.1600-0625.1992.tb00070.x.
Recent investigations indicate that malignant melanoma cells can produce distinct cytokines. While differences in the production of single cytokines have been observed among different melanoma cell lines, the extent of variability in the production of single and multiple cytokines between individual melanoma cell lines has not been as thoroughly investigated. A heterogeneity in melanoma cell cytokine production could have important implications for the biology of this aggressive neoplasm since certain cytokines may act as autocrine growth factors or be potent modulators of host immune response to the developing tumor. The purpose of this study is to assess the cytokine production profile of two widely available human melanoma cell lines, A375 and G361. The A375 cell line constitutively expressed the mRNA for IL-1 alpha, IL-1 beta and PDGF-A, with increased expression of these cytokines after induction with PMA. GM-CSF mRNA was expressed by the A375 melanoma line only after induction with PMA. No IL-6 mRNA was detected in the A375 melanoma cell line. The cell culture supernatants from the A375 cells likewise contained a parallel increase in IL-1 activity as determined in the D10 bioassay and secreted GM-CSF and PDGF-AA as measured by ELISA. In contrast, the G361 cell line did not express IL-1, GM-CSF or PDGF-A mRNA (constitutively or after PMA induction) but expressed only IL-6 mRNA and secreted IL-6 activity after PMA induction. These results demonstrate a significant heterogeneity in the production of IL-1 alpha, IL-1 beta, IL-6, GM-CSF, and PDGF in two distinct melanoma cell lines. This study demonstrates that individual melanoma cell lines express and secrete multiple cytokines both constitutively and after stimulation with PMA. The immunodulating and mitogenic properties of these melanoma-derived cytokines may have implications in determining the biologic behavior of different malignant melanomas.
近期研究表明，恶性黑色素瘤细胞能够产生不同的细胞因子。虽然在不同黑色素瘤细胞系中已观察到单一细胞因子产生的差异，但尚未对各个黑色素瘤细胞系之间单一及多种细胞因子产生的变异程度进行深入研究。黑色素瘤细胞细胞因子产生的异质性可能对这种侵袭性肿瘤的生物学特性具有重要意义，因为某些细胞因子可能作为自分泌生长因子，或者是宿主对正在形成的肿瘤免疫反应的强效调节剂。本研究的目的是评估两种广泛使用的人黑色素瘤细胞系A375和G361的细胞因子产生情况。A375细胞系组成性表达IL-1α、IL-1β和PDGF-A的mRNA，用佛波酯（PMA）诱导后这些细胞因子的表达增加。GM-CSF mRNA仅在A375黑色素瘤细胞系用PMA诱导后表达。在A375黑色素瘤细胞系中未检测到IL-6 mRNA。来自A375细胞的细胞培养上清液同样在D10生物测定中显示IL-1活性平行增加，并通过ELISA检测分泌GM-CSF和PDGF-AA。相比之下，G361细胞系不表达IL-1、GM-CSF或PDGF-A mRNA（组成性或PMA诱导后），但仅表达IL-6 mRNA并在PMA诱导后分泌IL-6活性。这些结果表明，在两种不同的黑色素瘤细胞系中，IL-1α、IL-1β、IL-6、GM-CSF和PDGF的产生存在显著异质性。本研究表明，各个黑色素瘤细胞系在组成性状态下以及用PMA刺激后均表达和分泌多种细胞因子。这些源自黑色素瘤的细胞因子的免疫调节和促有丝分裂特性可能对确定不同恶性黑色素瘤的生物学行为具有影响。
