Figure 9.

Hypothetical role of IL-6 in oncogenesis and tumor-associated thrombocytosis. IL-6 is produced in the tumor microenvironment both by mononuclear and tumor cells. Elevated levels of IL-6 induce thrombopoietin production in the liver, which in turn activates the maturation of megakaryocytes and the production of platelets resulting elevated platelet count. Simultaneously, IL-6 binds to the soluble form of IL-6 receptor (sIL-6R) and activates the gp130/JAK/STAT3 pathway leading to the translocation of phosphorylated STAT3 homodimer to the nucleus in the tumor cells and to the transcription of different genes inducing proliferation, cell growth and the inhibition of apoptosis. mIL-6R—membrane-bound IL-6 receptor, TPO—thrombopoietin, ADAM17—a disintegrin and metalloproteinase 17; STAT3—signal transducer and activator transcription 3.