Furthermore, we showed that Stat3 inhibitor significantly decreased the expression of MMP2 enhanced by IL-6, indicating that IL-6 promoted endometrial cancer invasion and migration by Stat3-induced MMP2 upregulation.
The molecular mechanism defined in this study provided the evidence that E2 promotes endometrial carcinoma progression via activating the IL-6 pathway, indicating that interruption of IL-6 might be an essential therapeutic strategy in estrogen-dependent endometrial cancer.
We show that a single amino acid exchange variant (G32R) of meprin β, identified in endometrium cancer, is more active against a peptide substrate and the IL-6 receptor than wild-type meprin β.
In vitro and in vivo experiments revealed that tumor-derived G-CSF and G-CSF-mediated IL-6 production from the tumor microenvironment are involved in the development of leukocytosis and thrombocytosis in patients with endometrial cancer.
Secretion of the cytokines CCL5, CCL2 and IL-6 increased after paclitaxel treatment in several endometrial cancer cell lines, but no general effect on cytokine secretion was detected after heparin treatment.
Taken together, these data indicate that IL-6 promotes endometrial carcinoma growth through an expanded autocrine regulatory loop and implicate the ERK-NF-κB pathway as a critical mediator of IL-6 production, implying IL-6 to be an important therapeutic target in endometrial carcinoma.
High serum levels of interleukin-6 in endometrial carcinoma are associated with uterine serous papillary histology, a highly aggressive and chemotherapy-resistant variant of endometrial cancer.