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Oncotarget: Diabetes mellitus is associated with liver metastasis of colorectal cancer


Oncotarget recently published "Diabetes mellitus is associated with liver metastasis of colorectal cancer through production of biglycan-rich cancer stroma" which reported that In this study, the authors investigated the relationship between the presence of diabetes mellitus and the progression and liver metastasis of CRC.

Histopathological findings in the primary lesions, which were preferential to diabetes-complicated CRC and the liver metastasis, were also investigated.

Histopathological findings correlated with liver metastasis in DM-CRC, including budding grade, perineural invasion, and myxomatous tumor stroma, and all were highly correlated with the stage.

Additionally, myxomatous stroma showed the strongest correlation with liver metastasis in multivariate analysis.

Myxomatous stroma in stage III cases correlated with liver recurrence.

Dr. Hiroki Kuniyasu from The Nara Medical University said, "Diabetes mellitus is a social problem in developed countries due to its frequency and the diversity and severity of its complications."

In recent years, attention has been focused on the relationship between diabetes and cancer, with the latter being one of the various complications observed in patients with diabetes.

Figure 4: Biglycan expression and epithelial-mesenchymal transition (EMT). (A) Biglycan protein expression and phosphorylated AKT level in HT29 cells treated with glucose (100 mg/dL or 450 mg/dL), elaidic acid (70 μM) or linoleic acid (20 μg/ml) and/or insulin (1 μg/mL) for 24 h. (B) Effect of biglycan (BGN) siRNA or control siRNA (C) on EMT-associated proteins (E-cadherin, Claudin-4, and Snail) and stemness-associated protein (CD44) in HT29 cells. (C) Effect of BGN siRNA (siBGN) or control siRNA (siCont) on cell proliferation of HT29 cells. (D) Number of liver metastasis of HT29 human colon cancer cells in nude mice. HT29 cells (1 × 106) pretreated with BGN siRNA or control siRNA (C) were inoculated into the spleen with or without mixed mesenchymal stem cells (MSC, 2 × 105). Error bar, standard deviation.

People with diabetes have an increased risk of carcinogenesis in most organs, including liver, pancreas, colorectum, stomach, breast, lung, oral cavity, and endometrium, and increased risk of associated mortality.

The causes of increased carcinogenic risk in diabetes include increased oxidative stress, high levels of insulin, related growth factors, and its binding factors, insulin receptor substrate-1 and their downstream phosphoinositide 3-kinase, AKT, mitogen-activated protein kinase signal, AMP-activated kinase, mammalian target of rapamycin, sirtuin 1, and autophagy signal activation.

Therefore, it is important to elucidate the relationship between diabetes and liver metastasis of CRC.

Here, the Oncotarget authors aimed to clarify the relationship between diabetes and CRC metastasis, especially liver metastasis via histopathological examinations.

The Oncotarget authors aimed to clarify the relationship between diabetes and CRC metastasis, especially liver metastasis via histopathological examinations.

The Kuniyasu Research Team concluded in their Oncotarget Research Paper, "our study suggests that diabetes promotes liver metastasis of CRC via biglycan, which induces cancer stemness and EMT from interaction with MSCs. This novel mechanism is believed to promote cancer malignancy in various cancers complicated with diabetes. The results of our study indicate the importance of diabetes management in malignant tumors in diabetes patients. And it is emphasized the significance of biglycan as a hopeful therapeutic target in malignant tumors with diabetes."

DOI - https://doi.org/10.18632/oncotarget.27674

Full text - https://www.oncotarget.com/article/27674/text/

Correspondence to - Hiroki Kuniyasu - cooninh@zb4.so-net.ne.jp

Keywords - diabetes, liver metastasis, colorectal cancer, biglycan, mesenchymal stem cell

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