Toll-like receptors in human multiple myeloma: studies on the cellular interaction with bone marrow microenvironment components

Abstract

Expression and function of Toll-like receptors (TLRs) in a variety of human malignancies has recently become an amazing research focus. TLRs which comprise in humans a family of 10 members (TLR1-10) are mainly expressed on immune cells but many cancer cells including those of B cell malignancies especially multiple myeloma (MM) express them as well, highlighting the possible involvement of inflammatory responses in disease progression / pathogenesis. In support of the fact that inflammation could function as a double-edged sword in tumor condition, a few recent studies showed that triggering of TLRs in MM cells caused both positive and negative outcomes including induction of proliferation, cell death, drug resistance and immune escape. In MM, malignant plasma cells usually acquire resistance to apoptotic signals and most anti-neoplastic drugs due to adhesion to fibronectin (FN) and bone marrow cells (BMSCs) which are two important bone marrow microenvironment components. In the present research we first analyzed the expression pattern of TLRs in a large panel of human myeloma cell lines (HMCLs) and MM primary cells and then explored if activation of TLRs in MM cells could have any effect on expression of adhesion molecules, adhesion to FN and BMSCs, and drug sensitivity of MM cells in the context of above components. We found that MM cells expressed a wide range of TLRs and that TLR triggering differentially modulated surface expression of adhesion molecules and adhesion to FN and BMSCs. Furthermore, TLR activation increased drug sensitivity of MM cells in the above context