Diabetes-associated angiotensin activation enhances liver metastasis of colon cancer.

Clinical & Experimental Metastasis
Takasumi ShimomotoHiroki Kuniyasu

Abstract

We examined the effects of hyperglycemic conditions on liver metastasis of colorectal cancer (CRC). Angiotensin (A)-II increased growth, invasion, and anti-apoptotic survival in HT29 and CT26 cells. In contrast, angiotensinogen (ATG) increased these features in HT29 cells but not in CT26 cells. HT29 cells expressed A-II type 1 receptor, chymase, and rennin, whereas CT26 cells did not express renin. Renin expression and ATG-induced cell growth, invasion, and survival induced and increased as glucose concentration increased in HT29 cells and also CT26 cells. An inhibitor of renin or chymase abrogated A-II production in HT29 cells. Reduction of hepatic ATG production by cholesterol-conjugated antisense S-oligodeoxynucleotide suppressed liver metastasis of HT29 cells. An examination of 121 CRC patients showed that diabetes in CRC cases was associated with higher blood HbA1c, higher renin and A-II concentrations in the primary tumors, and higher incidence of liver metastasis than in nondiabetic cases. These results suggest that diabetes-associated angiotensin activation enhances liver metastasis of CRC and may therefore provide a possible target for antimetastatic therapy in CRC.

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Citations

Jul 19, 2013·International Journal of Molecular Sciences·Takahiro KochiHisataka Moriwaki
Jun 18, 2015·Cancer Science·Yi LuoHiroki Kuniyasu
Jan 17, 2015·International Journal of Colorectal Disease·W Kurtis Childers
Dec 3, 2014·Diabetes Research and Clinical Practice·Ugo FedeliMario Saugo
Dec 20, 2018·Oncotarget·Sayako Matsushima-OtsukaHiroki Kuniyasu
May 21, 2020·International Journal of Molecular Sciences·Aldona Kasprzak, Agnieszka Adamek
Mar 7, 2021·Cells·Maksymilian ZiajaAgnieszka Wanda Piastowska-Ciesielska
Jun 3, 2021·International Journal of Molecular Sciences·Shingo KishiHiroki Kuniyasu

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