An Orchestrated Response To Tumor Signals By Macrophages and Mesenchymal Stem Cells Potentiates Interleukin-6 Secretion In Glioblastoma

Abstract

AbstractThe tumor microenvironment plays a critical role in the survival, growth, invasion, and metastasis of solid tumors. However, the mechanisms by which it influences these aspects of tumor progression remain incompletely characterized. In this study, we show that human glioblastoma cells secrete soluble factors that alter the phenotype and cytokine secretion profile of both macrophages and mesenchymal stem cells (MSCs). Macrophages and MSCs respond to tumor-secreted factors by increasing the release of interleukin-6 (IL-6) and this response is potentiated when macrophages and MSCs are combined in co-culture. In glioblastoma, IL-6 has been associated with tumor cell invasion, angiogenesis, tumor cell proliferation, immune suppression, and poor prognosis. Our results suggest that the orchestrated response of macrophages and stromal elements to neoplastic cells enhances tumor progression through the release of soluble factors.