Diabetes-associated angiotensin activation enhances liver metastasis of colon cancer. 2012

Takasumi Shimomoto, and Hitoshi Ohmori, and Yi Luo, and Yoshitomo Chihara, and Ayumi Denda, and Tomonori Sasahira, and Naokuni Tatsumoto, and Kiyomu Fujii, and Hiroki Kuniyasu
Department of Molecular Pathology, Nara Medical University, Shijo-cho, Kashihara, Nara, Japan.

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.

UI MeSH Term Description Entries
D008113 Liver Neoplasms Tumors or cancer of the LIVER. Cancer of Liver,Hepatic Cancer,Liver Cancer,Cancer of the Liver,Cancer, Hepatocellular,Hepatic Neoplasms,Hepatocellular Cancer,Neoplasms, Hepatic,Neoplasms, Liver,Cancer, Hepatic,Cancer, Liver,Cancers, Hepatic,Cancers, Hepatocellular,Cancers, Liver,Hepatic Cancers,Hepatic Neoplasm,Hepatocellular Cancers,Liver Cancers,Liver Neoplasm,Neoplasm, Hepatic,Neoplasm, Liver
D008297 Male Males
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008819 Mice, Nude Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses. Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D009361 Neoplasm Invasiveness Ability of neoplasms to infiltrate and actively destroy surrounding tissue. Invasiveness, Neoplasm,Neoplasm Invasion,Invasion, Neoplasm
D012083 Renin A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC 3.4.99.19. Angiotensin-Forming Enzyme,Angiotensinogenase,Big Renin,Cryorenin,Inactive Renin,Pre-Prorenin,Preprorenin,Prorenin,Angiotensin Forming Enzyme,Pre Prorenin,Renin, Big,Renin, Inactive
D003110 Colonic Neoplasms Tumors or cancer of the COLON. Cancer of Colon,Colon Adenocarcinoma,Colon Cancer,Cancer of the Colon,Colon Neoplasms,Colonic Cancer,Neoplasms, Colonic,Adenocarcinoma, Colon,Adenocarcinomas, Colon,Cancer, Colon,Cancer, Colonic,Cancers, Colon,Cancers, Colonic,Colon Adenocarcinomas,Colon Cancers,Colon Neoplasm,Colonic Cancers,Colonic Neoplasm,Neoplasm, Colon,Neoplasm, Colonic,Neoplasms, Colon
D003920 Diabetes Mellitus A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D006442 Glycated Hemoglobin Products of non-enzymatic reactions between GLUCOSE and HEMOGLOBIN (occurring as a minor fraction of the hemoglobin of ERYTHROCYTES.) It generally refers to glycated HEMOGLOBIN A. Hemoglobin A1c (Hb A1c) is hemoglobin A with GLYCATION on a terminal VALINE of the beta chain. Glycated hemoglobin A is used as an index of the average blood sugar level over a lifetime of erythrocytes. Fructated Hemoglobins,Glycohemoglobin,Glycohemoglobin A,Glycohemoglobins,Glycosylated Hemoglobin A,Hb A1c,HbA1,Hemoglobin A(1),Hemoglobin A, Glycosylated,Glycated Hemoglobin A,Glycated Hemoglobin A1c,Glycated Hemoglobins,Glycosylated Hemoglobin A1c,Hb A1,Hb A1a+b,Hb A1a-1,Hb A1a-2,Hb A1b,Hemoglobin, Glycated A1a-2,Hemoglobin, Glycated A1b,Hemoglobin, Glycosylated,Hemoglobin, Glycosylated A1a-1,Hemoglobin, Glycosylated A1b,A1a-1 Hemoglobin, Glycosylated,A1a-2 Hemoglobin, Glycated,A1b Hemoglobin, Glycated,A1b Hemoglobin, Glycosylated,Glycated A1a-2 Hemoglobin,Glycated A1b Hemoglobin,Glycosylated A1a-1 Hemoglobin,Glycosylated A1b Hemoglobin,Glycosylated Hemoglobin,Hemoglobin A, Glycated,Hemoglobin A1c, Glycated,Hemoglobin A1c, Glycosylated,Hemoglobin, Glycated,Hemoglobin, Glycated A1a 2,Hemoglobin, Glycosylated A1a 1,Hemoglobins, Fructated,Hemoglobins, Glycated

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