Interleukin 6 (IL‐6) and its receptor: Their role in plasma cell neoplasias

Abstract

Interleukin 6 (IL-6) is a multifunctional cytokine regulating immune response acute phase reaction and hematopoiesis. IL-6 plays a critical role in B cell differentiation to plasma cells and is a potent growth factor for plasmacytoma and myeloma. Abnormal production of IL-6 has been suggested to be involved in polyclonal plasma cell abnormalities and plasma cell neoplasias. The deregulated expression of the IL-6 gene in transgenic mice resulted in the generation of malignant plasmacytoma. Based on these findings, it could be considered that continuous IL-6 gene expression plays an essential role in a multistep oncogenesis of plasma cell neoplasias. The role of IL-6 and its receptor in the generation of plasma cell neoplasias and the mechanisms of the IL-6 gene expression and IL-6 receptor-mediated signal transduction are described.

Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors

“…Overexpression of IL-6 in transgenic mice induces polyclonal plasmacytosis (Suematsu et al, 1989), and ± depending on the genetic background of the mice ± plasmacytoma develops eventually (Suematsu et al, 1992). These observations suggested a critical role for IL-6 in plasmacytomagenesis (Hirano, 1991). Consistent with this, it was found that IL-6 is essential for raf/myc plasma cell tumor induction (Hilbert et al, 1995a).…”

The combination of the farnesyl transferase inhibitor lonafarnib and the proteasome inhibitor bortezomib induces synergistic apoptosis in human myeloma cells that is associated with down-regulation of p-AKT

“…16,27 IL-6-mediated growth and proliferation is mediated by the Ras/Raf/MAPK pathway, a known target for the FTIs. 28,29 To date several FTIs have been evaluated in preclinical and clinical trials, 30 including BMS-214664, L-778123, R115777 (tipifarnib), and SCH-66336 (lonafarnib). Overall, FTIs have been shown to have mild toxicities, but also modest activity with the exception of acute myeloid leukemia (AML).…”

GLI2 Transcription Factor Mediates Cytokine Cross-talk in the Tumor Microenvironment

“…1A). IL-6 is a proinflammatory cytokine shown to be important for the biology of normal and malignant B cells (10,(31)(32)(33)(34)(35)(36)(37)(38)(39). Characterization of this phenomenon revealed that CCL5-induced IL-6 secretion was accompanied by an increase in IL-6 mRNA levels and promoter activity (Fig.…”

“…Malignant B cells at various stages of development depend on signaling from the surrounding microenvironment to survive and proliferate within the host and promote chemoresistance (3)(4)(5)(6). Bone marrow stromal cells provide malignant B cells with external signals such as soluble growth factors, antigens, cytokines, and cell-cell interactions (7)(8)(9)(10)(11). Therefore, a better understanding of the crosstalk between malignant cells and stromal cells will be essential for the development of new therapies targeting B cell malignancies.…”