Mattei S, Colombo M P, Melani C, Silvani A, Parmiani G, Herlyn M
Istituto Nazionale Tumori, Milan, Italy.
Int J Cancer. 1994 Mar 15;56(6):853-7. doi: 10.1002/ijc.2910560617.
Human tumors can constitutively express cytokines and growth factors, but the extent of this expression has not been investigated. Using 44 different probes to cytokines, growth factors, and their receptors, we tested 21 melanoma and 5 melanocyte cultures for RNA transcript expression by reverse transcriptase-polymerase chain reaction. With 30 amplification cycles, expression of the cytokines interleukin (IL)-1 beta, IL-6, leukemia inhibitory factor (LIF), IL-7, gro alpha, IL-8 and the p35 chain of IL-12 was detected in more than 60% of melanomas. Concomitant receptors for IL-6 and IL-7 were also detected. IL-1 alpha, IL-5, Rantes, IL-10, interferon (IFN)-beta, tumor-necrosis factor (TNF)-alpha, G-colony-stimulating factor (CSF) and GM-CSF were expressed at lower levels. Melanocytes showed greatly reduced cytokine RNA transcripts, and only gro alpha was consistently detected. No expression of IL-2, IL-3, IL-4, IL-9, the p40 chain of IL-12, IFN-alpha or IFN-gamma RNA transcripts was detected in melanomas or melanocytes. The growth factors expressed by melanomas and, after further signal amplification, by melanocytes were transforming growth factor (TGF)-alpha, epidermal growth factor (EGF), TGF-beta, endothelial-cell growth factor (ECGF), basic-fibroblast growth factor (bFGF), nerve growth factor (NGF) and steel. The receptors EGFR, FGFR, NGFRp70 and c-kit were also expressed by melanomas and melanocytes. These results point to new possible autocrine and paracrine pathways in melanoma biology.
人类肿瘤能够组成性地表达细胞因子和生长因子,但其表达程度尚未得到研究。我们使用针对细胞因子、生长因子及其受体的44种不同探针,通过逆转录聚合酶链反应检测了21种黑色素瘤培养物和5种黑素细胞培养物的RNA转录本表达。经过30个扩增循环,在超过60%的黑色素瘤中检测到细胞因子白细胞介素(IL)-1β、IL-6、白血病抑制因子(LIF)、IL-7、groα、IL-8以及IL-12的p35链的表达。同时还检测到了IL-6和IL-7的相应受体。IL-1α、IL-5、趋化因子RANTES、IL-10、干扰素(IFN)-β、肿瘤坏死因子(TNF)-α、粒细胞集落刺激因子(G-CSF)和粒细胞巨噬细胞集落刺激因子(GM-CSF)的表达水平较低。黑素细胞显示出细胞因子RNA转录本大幅减少,仅持续检测到groα。在黑色素瘤或黑素细胞中未检测到IL-2、IL-3、IL-4、IL-9、IL-12的p40链、IFN-α或IFN-γRNA转录本的表达。黑色素瘤以及经过进一步信号放大后的黑素细胞所表达的生长因子有转化生长因子(TGF)-α、表皮生长因子(EGF)、TGF-β、内皮细胞生长因子(ECGF)、碱性成纤维细胞生长因子(bFGF)、神经生长因子(NGF)和干细胞因子。黑色素瘤和黑素细胞还表达了受体表皮生长因子受体(EGFR)、成纤维细胞生长因子受体(FGFR)、神经生长因子受体p70(NGFRp70)和原癌基因c-kit。这些结果指出了黑色素瘤生物学中新的可能的自分泌和旁分泌途径。