Clinical & Experimental Metastasis

, Volume 23, Issue 3–4, pp 203–208

Expression of a metastatic phenotype in IFNs-primed/TNFα-activated B16 murine melanoma cells: role of JAK1/PKCδ signal transduction factors

  • Francesca Bianchini
  • Antonella Mannini
  • Gabriele Mugnai
  • Salvatore Ruggieri
  • Lido Calorini
Original Research Paper

Abstract

In previous studies, we found that IFNγ and TNFα generated by activated macrophages stimulate the metastatic potential in F10-M3 cells, a clone isolated from B16-F10 murine melanoma line. In this phenomenon, TNFα promoted the expression of a metastatic phenotype in tumor cells previously primed with IFNγ. Here, we demonstrate that IFNα or IFNβ may replace IFNγ in priming tumor cells. We also noticed that an enhancement of the expression of p55TNFα receptor was associated with the preconditioning of tumor cells with IFNγ and IFNβ. 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 p55TNFα receptor shown in IFNγ- and IFNβ-primed melanoma cells stimulated with TNFα. Furthermore, the activity of the protein kinase C (PKC) was required for IFNγ-primed melanoma cells to express a metastatic phenotype after stimulation with TNFα. In conclusion, our study shows that a metastatic phenotype was expressed in B16 murine melanoma cells stimulated with TNFα regardless of whether the cells were primed with IFNγ IFNα or IFNβ. The molecular events leading to the expression of a metastatic phenotype in F10-M3 melanoma cells are represented by: (a) an enhanced expression of p55TNFα receptor in IFNs-primed tumor cells dependent on JAK1 signal transduction pathway; and (b) an intact PKC activity during TNFα stimulation.

Keywords

F10-M3 murine melanoma cells Metastatic phenotype IFNα,β,γ TNFα JAK1 PKCδ JAK inhibitor I Rottlerin 

Copyright information

© Springer Science + Business Media B.V. 2006

Authors and Affiliations

  • Francesca Bianchini
    • 1
  • Antonella Mannini
    • 1
  • Gabriele Mugnai
    • 1
  • Salvatore Ruggieri
    • 1
  • Lido Calorini
    • 1
  1. 1.Dipartimento di Patologia e Oncologia SperimentaliUniversità degli Studi di FirenzeFirenzeItaly

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