Expression of a metastatic phenotype in IFNs-primed/TNFalpha-activated B16 murine melanoma cells: role of JAK1/PKCdelta signal transduction factors.
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.
Bianchini
Francesca
F
Dipartimento di Patologia e Oncologia Sperimentali, Università degli Studi di Firenze, V.le G.B. Morgagni 50, 50134, Firenze, Italy.
Mannini
Antonella
A
Mugnai
Gabriele
G
Ruggieri
Salvatore
S
Calorini
Lido
L
D000818:Animals; D045744:Cell Line, Tumor; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D053612:Janus Kinases / Q000502:physiology*; D008175:Lung Neoplasms / Q000556:secondary; D008546:Melanoma, Experimental / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D053612:Janus Kinases