Thrombopoietic Cytokine Circuit Fuels Ovarian Tumor Growth
(HealthDay News) – In patients with ovarian cancer and in a related mouse model, a paracrine loop involving increased hepatic thrombopoietin and tumor-derived interleukin-6 increases platelet counts and promotes tumor growth, according to a study published in the Feb. 16 issue of the New England Journal of Medicine.
To investigate the association between platelet counts and disease outcome, Rebecca L. Stone, MD, from the University of Texas MD Anderson Cancer Center in Houston, and colleagues analyzed clinical data on 619 patients with epithelial ovarian cancer. Human samples and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis.
The researchers found that thrombocytosis correlated significantly with advanced disease and shortened survival. Compared to those without thrombocytosis, in patients with thrombocytosis, plasma levels of thrombopoietin and interleukin-6 were significantly increased. Elevated hepatic thrombopoietin synthesis was an underlying mechanism of paraneoplastic thrombocytosis, in response to tumor-derived interleukin-6, in mouse models. In tumor-bearing mice, thrombocytosis was abrogated by silencing thrombopoietin and interleukin-6. In tumor-bearing mice and patients with epithelial ovarian cancer, treatment with anti-interleukin-6 antibody significantly reduced platelet counts. In mouse models of epithelial ovarian cancer, neutralizing interleukin-6 significantly improved the therapeutic efficacy of paclitaxel. In tumor-bearing mice, use of an antiplatelet antibody that halved platelet counts significantly reduced tumor growth and angiogenesis.
"These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis, which fuels tumor growth," the authors write.
One of the authors is listed as an inventor on a U.S. patent pertaining to the study.