Mesenchymal stromal cells regulate M2 macrophage polarization that promotes proliferation, migration, and invasion of renal cell carcinoma cells.

Accumulating evidence from studies in other tumour types suggests that mesenchymal stromal cells (MSCs) may influence macrophage polarization, but the underlying mechanisms in renal cell carcinoma (RCC) remain unclear. In this study, renal carcinoma-derived MSCs (RCC-MSCs) were isolated from the tumour tissue of a patient with clear cell renal cell carcinoma, and BM-MSC-derived MSC1 was included as an exploratory reversal model rather than as a biologically matched comparator. THP-1-derived macrophage models, together with co-culture assays, flow cytometry, Western blotting, quantitative real-time PCR, and ELISA, were used to evaluate macrophage phenotypes and cytokine secretion. Patient-derived RCC-MSCs from a single ccRCC specimen promoted M2-like macrophage polarization in vitro, and this effect was attenuated by NF-κB inhibition with pyrrolidine dithiocarbamate (PDTC). In turn, RCC-MSC-primed macrophages enhanced the growth, migration, and invasion of 786-O cells in vitro, whereas blockade of NF-κB attenuated these tumour-promoting effects. In an exploratory in vitro setting, BM-MSC-derived MSC1 favoured partial reprogramming of M2 macrophages toward an M1-like phenotype. Collectively, these findings suggest that patient-derived RCC-MSCs from a single ccRCC specimen may promote M2-like macrophage polarization through NF-κB-related signalling and enhance malignant phenotypes of 786-O cells in vitro, while BM-MSC-derived MSC1 supports the plasticity of macrophage polarization in an exploratory setting.