Interleukin-6 As An Enhancer of Anti-Angiogenic Therapy for Ovarian Clear Cell Carcinoma.

Abstract

Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer (EOC) and associated with elevated interleukin-6 (IL-6) expression, resistance to chemotherapy, and increased mortality. Although bevacizumab (Bev) is a widely used anti-angiogenic agent for EOC, the efficacy of Bev and the role of IL-6 in modulating angiogenesis in OCCC are unknown. We performed tube formation assays on human umbilical vein endothelial cells (HUVEC) cultured in OCCC conditioned media and in direct co-culture with OCCC cells and observed that IL-6 inhibition significantly mitigated the ability of Bev to impede tube formation in both cases. Furthermore, the IL-6 blockade not only disrupted the anti-angiogenic efficacy of Bev but also the concomitant anti-tumor activity. We also found that IL-6 inhibition resulted in a significant increase in the secreted levels of angiopoietin-1 (Ang1) in addition to decreased vascular endothelial growth factor (VEGF) expression. Clinical specimens also exhibited this reciprocal relationship between IL-6 and Ang1 expression. Finally, knockdown of Ang1 prevented IL-6 inhibition from mitigating the effects of Bev, demonstrating that IL-6 supports the anti-angiogenic activity of Bev by suppressing Ang1 and promoting dependence on VEGF for angiogenesis. Altogether, our data suggest that OCCC tumors with high IL-6 are candidates for Bev therapy.

Modulation of anti-angiogenic activity using ultrasound-activated nutlin-loaded piezoelectric nanovectors

“…In addition, Seki et al. showed that IL-6 inhibition leads to reduced anti-angiogenic activity in co-cultures of ovarian clear cell carcinoma (OCCC) cells and HUVECs by increasing angiopoietin-1 (Ang1) secretion and reducing VEGF expression [ 59 ]. It can be considered that IL-6 regulates VEGF synthesis, and thus its anti-angiogenic activity may be indirect.…”

Novel therapeutic strategies for injured endometrium: Autologous intrauterine transplantation of menstrual blood-derived cells from infertile patients

“…The procedure was followed and modified as previously reported 35 . Briefly, human umbilical vein endothelial cells (HUVECs, ATCC, Cat# CRL-1730) were incubated with endothelial cell medium (ECM) (Sciencell Research Laboratory, CA, 1001) at passage 6-8 when the cells reached to 80-100% confluency.…”

O3C Glass-Class: A Machine-Learning Framework for Prognostic Prediction of Ovarian Clear-Cell Carcinoma

“…3 Both histopathology and FIGO staging are considered the gold standard for classification of EOC subgroups and are relevant prognostic factors for stratification. 4 Many studies have explored the molecular mechanisms underlying this malignancy, 5,6 however, accurate prediction of treatment outcome and anticipated personalized prognosis is still lacking. 7,8…”

“…3 Both histopathology and FIGO staging are considered the gold standard for classification of EOC subgroups and are relevant prognostic factors for stratification. 4 Many studies have explored the molecular mechanisms underlying this malignancy, 5,6 however, accurate prediction of treatment outcome and anticipated personalized prognosis is still lacking. 7,8 Among the histotypes of EOC, ovarian clear cell carcinoma (OCCC) exhibits unique clinicopathological and molecular features, and therefore is recognized as a distinct entity, presenting unique challenges for treatment.…”