[HTML][HTML] Interleukin-6 released by colon cancer-associated fibroblasts is critical for tumour angiogenesis: Anti-interleukin-6 receptor antibody suppressed …
T Nagasaki, M Hara, H Nakanishi, H Takahashi… - British journal of …, 2014 - nature.com
T Nagasaki, M Hara, H Nakanishi, H Takahashi, M Sato, H Takeyama
British journal of cancer, 2014•nature.comBackground: Interleukin-6 (IL-6) has an important role in cancer progression, and high levels
of plasma IL-6 are correlated with a poor prognosis in a variety of cancers. It has also been
reported that tumour stromal fibroblasts are necessary for steps in cancer progression, such
as angiogenesis. There have been few reports of a correlation between fibroblast actions
and IL-6 levels. In this study, we examined the correlation between cancer stromal
fibroblasts and IL-6 and the utility of IL-6 as a therapeutic target in human colon cancer …
of plasma IL-6 are correlated with a poor prognosis in a variety of cancers. It has also been
reported that tumour stromal fibroblasts are necessary for steps in cancer progression, such
as angiogenesis. There have been few reports of a correlation between fibroblast actions
and IL-6 levels. In this study, we examined the correlation between cancer stromal
fibroblasts and IL-6 and the utility of IL-6 as a therapeutic target in human colon cancer …
Abstract
Background:
Interleukin-6 (IL-6) has an important role in cancer progression, and high levels of plasma IL-6 are correlated with a poor prognosis in a variety of cancers. It has also been reported that tumour stromal fibroblasts are necessary for steps in cancer progression, such as angiogenesis. There have been few reports of a correlation between fibroblast actions and IL-6 levels. In this study, we examined the correlation between cancer stromal fibroblasts and IL-6 and the utility of IL-6 as a therapeutic target in human colon cancer.
Methods:
The expression levels of IL-6 and VEGF of fibroblasts and cancer cell lines were evaluated using real-time PCR and ELISA. The anti-angiogenic effect of inhibiting IL-6 signalling was measured in an angiogenesis model and animal experiment.
Results:
We demonstrate that stromal fibroblasts isolated from colon cancer produced significant amounts of IL-6 and that colon cancer cells enhanced IL-6 production by stromal fibroblasts. Moreover, IL-6 enhanced VEGF production by fibroblasts, thereby inducing angiogenesis. In vivo, anti-IL6 receptor antibody targeting stromal tissue showed greater anti-tumour activity than did anti-IL6 receptor antibody targeting xenografted cancer cells.
Conclusion:
Cancer stromal fibroblasts were an important source of IL-6 in colon cancer. IL-6 produced by activated fibroblasts induced tumour angiogenesis by stimulating adjacent stromal fibroblasts. The relationship between IL-6 and stromal fibroblasts offers new approaches to cancer therapy.
nature.com