The role of angiotensin II in proliferation and fibrosis of peritoneal dissemination in gastric cancer.
Abstract
The renin–angiotensin system (RAS) plays an important role not only in homeostasis, but also in carcinogenesis. Recent studies have shown that a local RAS can exist in malignant tumor tissue, with angiotensin II potentially acting as a key factor for promotion of tumor growth and metastasis. We discuss the role of angiotensin II in proliferation and fibrosis of peritoneal dissemination in gastric cancer. We previously demonstrated the presence of a local angiotensin II/AT1 receptor generating system in human gastric cancer. Furthermore, three types of cascade for tumor progression with accompanying extensive stromal fibrosis in response to angiotensin II stimulation were identified: antiapoptosis pathway through NF-κB activation, cell proliferation through phosphorylation of ERK1/2, and fibrosis through TGF-β1-induced EMT. AT1 receptor blockers (ARBs) suppress tumor proliferation and fibrotic changes by impairing angiotensin II stimulation, and thus the above cascades, in a xenograft mouse model of fibrotic tumor. ARBs have been widely used as clinical antihypertensive agents without serious side effects, and recent study were reported that ARBs was associated with longer progression-free survival and overall survival in malignancy patients. ARB are expected to offer a new repositioning drug strategy for peritoneal dissemination in gastric cancer.
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DOI: http://dx.doi.org/10.18103/imr.v3i1.330
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