through the CCL2-dependent recruitment and polarization of monocytes Mesenchymal stromal cells orchestrate follicular lymphoma cell niche

Abstract Accumulating evidence indicates that infiltrating stromal cells contribute directly and indirectly to tumor growth in a wide range of cancers. In follicular lymphoma (FL), malignant B cells are found admixed with heterogeneous lymphoid-like stromal cells within invaded lymph nodes and bone marrow (BM). In addition, mesenchymal stromal cells (MSC) support in vitro FL B-cell survival, in particular after their engagement towards lymphoid differentiation. We show here that BM-MSC obtained from FL patients (FL-MSC) display a specific gene expression profile compared to MSC obtained from healthy age-matched donors (HD-MSC). This FL-MSC signature is significantly enriched for genes associated with a lymphoid-like commitment. Interestingly, CCL2 could be detected at a high level within FL cell niche, is upregulated in HD-MSC by coculture with malignant B cells, and is overexpressed by FL-MSC, in agreement with their capacity to recruit monocytes more efficiently than HD-MSC. Moreover, FL-MSC and macrophages cooperate to sustain malignant B-cell growth whereas FL-MSC drive monocyte differentiation towards a proangiogenic and LPS-unresponsive phenotype close to that of tumor-associated macrophages. Altogether, these results highlight the complex role of FL stromal cells that promote direct tumor B-cell growth and orchestrate FL cell niche, thus emerging as a potential therapeutic target in this disease. From bloodjournal.hematologylibrary.org by guest on March 5, 2013. For personal use only.

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