Supplementary Figures S1-S7 from Interleukin-6 Stimulates Defective Angiogenesis

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posted on 2023-03-30, 23:03 authored by Ganga Gopinathan, Carla Milagre, Oliver M.T. Pearce, Louise E. Reynolds, Kairbaan Hodivala-Dilke, David A. Leinster, Haihong Zhong, Robert E. Hollingsworth, Richard Thompson, James R. Whiteford, Frances Balkwill

Supplementary Figures S1-S7. Western blot quantification of pERK and pSTAT3 from aortic lysates (S1); Western blot quantification of pERK and pSTAT3 from MLEC lysates (S2); Western blot analysis and quantification of pERK and pSTAT3 from HUVEC lysates (S3); IL-6 reduces the expression of NG2 in the aortic ring vessels (S4); Regulation of Notch signaling and Angiopoietin2 by VEGF and IL-6 (S5); Effects of VEGF and IL-6 treatment on HUVEC (S6); Effects of anti-IL-6 antibody on in vivo IGROV-1 vasculature (S7).

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ARTICLE ABSTRACT

The cytokine IL6 has a number of tumor-promoting activities in human and experimental cancers, but its potential as an angiogenic agent has not been fully investigated. Here, we show that IL6 can directly induce vessel sprouting in the ex vivo aortic ring model, as well as endothelial cell proliferation and migration, with similar potency to VEGF. However, IL6-stimulated aortic ring vessel sprouts had defective pericyte coverage compared with VEGF-stimulated vessels. The mechanism of IL6 action on pericytes involved stimulation of the Notch ligand Jagged1 as well as angiopoietin2 (Ang2). When peritoneal xenografts of ovarian cancer were treated with an anti-IL6 antibody, pericyte coverage of vessels was restored. In addition, in human ovarian cancer biopsies, there was an association between levels of IL6 mRNA, Jagged1, and Ang2. Our findings have implications for the use of cancer therapies that target VEGF or IL6 and for understanding abnormal angiogenesis in cancers, chronic inflammatory disease, and stroke. Cancer Res; 75(15); 3098–107. ©2015 AACR.