Bone Marrow Adipocytes Influence Multiple Myeloma Development by Secretion of Different Growth Factors and Chemokines.

Abstract

In multiple myeloma (MM) monoclonal plasma cells accumulate in the bone marrow (BM) where they interact with neighboring cells to receive supportive signals. Since BM adipocytes are known to participate in normal and malignant hematopoiesis, we presumed interactions between BM adipocytes and myeloma cells. Using an adipocytic cell line and primary isolated BM adipocytes, we performed functional assays indicating that adipocytes support MM cell development by affecting proliferation, apoptosis, cell migration and adhesion. We subsequently analyzed the secretion of different cytokines by BM adipocytes and analyzed the contribution of a specific adipokine, leptin, to these processes. We confirmed the expression of leptin by adipocytes and leptin receptor by myeloma cells. Immunostaining showed strong presence of leptin receptor on MM cells in 13 of 28 patients tested. This expression was not correlated to disease stage. On cell proliferation, leptin acted as a moderate growth factor. We conclude that, next to the earlier described interactions within the BM, adipocytes influence MM cell behavior by affecting proliferation, apoptosis and migration and that part of these effects may be contributed to leptin.