Abstract 139: Interaction between monocytes and bone marrow microenvironment in pathogenesis of multiple myeloma

Abstract

Abstract Multiple myeloma (MM) is an incurable haematological malignancy characterized by the clonal proliferation of malignant plasma cells within the bone marrow. The current data on MM disease progression indicate that bone marrow microenvironment plays crucial role in pathogenesis of MM. Myeloma cells contacts with bone marrow stromal cells (BMSCs), which secrete factors/cytokines, promoting tumor cell growth and survival. Paracrine secretion of cytokines, such as IL-6, insulin-like growth factor-1, inflammatory protein-1a in BMSCs promotes MM cell proliferation and protects against drug-induced cytotoxicity. MM lytic bone disease is caused by osteoclast activation and osteoblast inhibition. Disease-related bone complications result in significant morbidity due to pain, pathologic fractures and spinal cord compression. The bone microenvironment creates a supportive niche for MM progression. Osteoclasts and BMSCs, along with extracellular matrix and cytokines stimulate myeloma cell proliferation and confer chemoresistance. Therefore, the reciprocal interactions among tumor cells, osteoclasts, osteoblasts, and bone marrow stromal cells impact both the establishment and progression of MM. In current study, monocyte can directly promote osteogenic differentiation of mesenchymal stem cells through cell contact interactions and production of osteogenic factors. This mechanism is mediated by the activation of STAT3 signaling pathway in the mesechymal stem cells that leads to the upregulation of osteoblasts-associated genes such as Runx2 and alkaline phosphatase (ALP), and the downregulation of osteoblast inhibitors such as DKK1 to drive the differentiation of mesechymal stem cells into osteoblasts. In this study, we examined the role of monocyte, a component of bone marrow microenvironment, in the MM progression. We investigated the proliferation of MM cell lines cultured alone or co-cultured with BMSCs and/or monocytes of MM patients. Consistently, we observed increased proliferation of MM cell lines in the presence of either BMSCs or monocytes compared to cell line-only control. Furthermore, the co-culture of BMSCs plus monocytes induced the greatest degree of proliferation of myeloma cells. In addition to increased proliferation, BMSCs and monocytes decreased the rate of apoptosis of myeloma cells. Our results therefore suggest that highlights the role of monocyte as an important component of the bone marrow microenvironment. Citation Format: Hiroshi Ikeda, Yuka Aoki, Toshiaki Hyayashi, Yumiko Maruyama, Tadao Ishida, Takashi Tokino, Yasuhisa Shinomura, Yasushi Sasaki. Interaction between monocytes and bone marrow microenvironment in pathogenesis of multiple myeloma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 139. doi:10.1158/1538-7445.AM2014-139