Role of Stat3 activation in cell-cell interaction between B-cell lymphoma and macrophages: the in vitro study

Recently, tumor-associated macrophages (TAMs) have been of interest because of their protumoral functions. In patients with malignant lymphoma, an increased number of alternatively activated (M2) macrophages is closely associated with poor clinical prognosis. Signal transducer and activator of transcription 3 (Stat3) is an important molecule related to tumor development. Previously we demonstrated that Stat3 activation in primary central nervous system lymphoma cells was significantly associated with the number of M2 TAMs present. Here we report that direct contact with macrophages in culture was required for proliferation of B-cell lymphoma cell lines, and that M2 macrophages induced more proliferation than did M1 macrophages. Stat3 activation in lymphoma cells was involved in this cell-cell interaction. Cytokine array analysis demonstrated that complement 5a (C5a) was detected in supernatants of M2 macrophages, but not in those of M1 macrophages or lymphoma cells. Although we demonstrated M2 macrophage-derived C5a is one of growth factors and a Stat3 activator, C5a was not a predominant molecule associated to lymphoma cell activation induced by M2 macrophages. However, these findings provide novel insights into the molecular mechanism related to M2 macrophages and lymphoma cell interaction.