학술논문

A potential role for hepcidin in obesity-driven colorectal tumourigenesis
Document Type
Report
Source
Oncology Reports. January, 2018, Vol. 39 Issue 1, p392, 9 p.
Subject
Cellular proteins -- Health aspects
Colorectal cancer -- Genetic aspects -- Development and progression -- Care and treatment
Language
English
ISSN
1021-335X
Abstract
The obesity epidemic is associated with increases in the incidence of several types of cancer, including colorectal cancer, and is associated with poor outcomes for patients. Adipose tissue is considered biologically active and represents a plausible link between cancer and obesity due to the many factors that it secretes. In the present study, human adipose tissue was cultured in vitro and predifferentiated adipocyte secretome [preadipocyte (PAS)] and differentiated adipocyte secretome (DAS) were collected. Quantification of interleukin-6 (IL-6), leptin and hepcidin in the DAS medium was compared to the PAS medium. Fold change levels of hepcidin, leptin and IL-6 in DAS (2.88[+ or -]0.28, 12.34[+ or -]0.95 and 31.29[+ or -]1.89 fold increases) were significantly higher compared to these in PAS (p=0.05). The SW480 colorectal cancer cells were co-cultured with DAS in the presence or absence of leptin, IL-6 or hepcidin inhibitors and cellular viability and proliferation assays were performed. The culture of SW480 with DAS increased the cell proliferation and viability by 30 and 15% (p=0.02 and p=0.03) respectively, which was reversed in the presence of inhibitors. Challenging the SW480 cells with IL-6 or hepcidin significantly elevated colonocyte-secreted leptin (p=0.05). Challenging the SW480 cells with leptin or hepcidin resulted in elevated levels of colonocyte-secreted IL-6 (p=0.05). Similarly, challenging cells with either IL-6 or leptin markedly elevated the level of secreted hepcidin (p=0.05) and this was associated with an induction in colonocyte iron levels in both cases. Collectively, these data revealed that adipocyte-secreted factors can ultimately modulate colonocyte iron levels and phenotype. Key words: iron, cancer, interleukin-6, leptin, adipokine
Introduction A quarter of adults worldwide are classified as obese [(body mass index (BMI), [greater than or equal to]30 kg/[m.sup.2])] (1), with projections that this will increase to a third [...]