Expression of STAT3 and its phosphorylated forms in mantle cell lymphoma cell lines and tumours

The pathogenesis of mantle cell lymphoma (MCL) is incompletely understood, although cyclin D1 overexpression leading to deregulated cell proliferation is probably important. Recent data suggest that interleukin (IL)-10 can increase the proliferative activity of MCL cells. STAT3 (signal transducer and activator of transcription 3) is the signal transducer of IL-10, and STAT3 is activated by phosphorylation. The hypothesis of this study is that STAT3 is activated in MCL. The expression of the two phosphorylated (i.e. active) forms of STAT3, pSTAT3-tyr (phosphorylated at the tyrosine(705) residue) and pSTAT3-ser (phosphorylated at the serine(727) residue), was assessed in four MCL cell lines and 12 MCL tumours using western blots and/or immunofluorescence staining techniques. All MCL cell lines expressed STAT3, but only one had detectable pSTAT3-tyr and none had pSTAT3-ser. Addition of IL-10 rapidly resulted in expression of pSTAT3-tyr but not pSTAT3-ser. All eight cases of frozen MCL tumours examined had detectable pSTAT3-tyr and pSTAT3-ser. Immunofluorescence studies using four formalin-fixed, paraffin wax-embedded MCL tumours demonstrated cytoplasmic localization of STAT3, as opposed to the nuclear localization of the pSTAT3 species. In conclusion, these findings provide evidence that STAT3 is constitutively activated in MCL, supporting the concept that STAT3 signalling may be important in the pathogenesis of these tumours.