Bianchini Francesca, Mannini Antonella, Mugnai Gabriele, Ruggieri Salvatore, Calorini Lido
Dipartimento di Patologia e Oncologia Sperimentali, Università degli Studi di Firenze, V.le G.B. Morgagni 50, 50134, Firenze, Italy.
Clin Exp Metastasis. 2006;23(3-4):203-8. doi: 10.1007/s10585-006-9030-1. Epub 2006 Sep 22.
In previous studies, we found that IFNgamma and TNFalpha generated by activated macrophages stimulate the metastatic potential in F10-M3 cells, a clone isolated from B16-F10 murine melanoma line. In this phenomenon, TNFalpha promoted the expression of a metastatic phenotype in tumor cells previously primed with IFNgamma. Here, we demonstrate that IFNalpha or IFNbeta may replace IFNgamma in priming tumor cells. We also noticed that an enhancement of the expression of p55TNFalpha receptor was associated with the preconditioning of tumor cells with IFNgamma and IFNbeta. By the use of an appropriate inhibitor, we observed that JAK1 signal transduction pathway was involved in the expression of a metastatic phenotype and of p55TNFalpha receptor shown in IFNgamma- and IFNbeta-primed melanoma cells stimulated with TNFalpha. Furthermore, the activity of the protein kinase C (PKC) was required for IFNgamma-primed melanoma cells to express a metastatic phenotype after stimulation with TNFalpha. In conclusion, our study shows that a metastatic phenotype was expressed in B16 murine melanoma cells stimulated with TNFalpha regardless of whether the cells were primed with IFNgamma IFNalpha or IFNbeta. The molecular events leading to the expression of a metastatic phenotype in F10-M3 melanoma cells are represented by: (a) an enhanced expression of p55TNFalpha receptor in IFNs-primed tumor cells dependent on JAK1 signal transduction pathway; and (b) an intact PKC activity during TNFalpha stimulation.
在先前的研究中，我们发现活化巨噬细胞产生的γ干扰素（IFNγ）和肿瘤坏死因子α（TNFα）可刺激F10-M3细胞的转移潜能，F10-M3细胞是从B16-F10小鼠黑色素瘤细胞系中分离出的一个克隆。在这一现象中，TNFα促进了先前经IFNγ预处理的肿瘤细胞中转移表型的表达。在此，我们证明α干扰素（IFNα）或β干扰素（IFNβ）在预处理肿瘤细胞时可替代IFNγ。我们还注意到，p55TNFα受体表达的增强与肿瘤细胞经IFNγ和IFNβ预处理有关。通过使用合适的抑制剂，我们观察到JAK1信号转导通路参与了经TNFα刺激的IFNγ和IFNβ预处理的黑色素瘤细胞中转移表型和p55TNFα受体的表达。此外，蛋白激酶C（PKC）的活性是IFNγ预处理的黑色素瘤细胞在经TNFα刺激后表达转移表型所必需的。总之，我们的研究表明，无论细胞是经IFNγ、IFNα还是IFNβ预处理，用TNFα刺激的B16小鼠黑色素瘤细胞都会表达转移表型。导致F10-M3黑色素瘤细胞中转移表型表达的分子事件表现为：（a）依赖JAK1信号转导通路的IFN预处理肿瘤细胞中p55TNFα受体表达增强；（b）TNFα刺激期间PKC活性完整。
