Abstract
BackgroundContradictory results are reported for the role of angiopoietin-like 4 (ANGPTL-4) in the development of cancer-cachexia and inflammation, given its importance in angiogenesis and inflammatory signaling. Our aim was to analyze the levels of ANGPTL-4 in colorectal cancer patients with a stable weight and those with cachexia in order to establish a relationship between ANGPTL-4 and the inflammatory process.ResultsPlasma and tumor levels of ANGPTL-4 were higher in CC in comparison to other groups. A positive association was verified between plasmatic ANGPTL-4 and NFκB levels in tumor from CC. In WSC, we identified an association between the plasmatic ANGPTL-4, IL-15, and IL-10 in tumor and IL-15 in MES. Increased levels of NFκB and TNF-R1 in MES were detected in CC in comparison to WSC. Specifically in CC-group, a positive correlation was found between ANGPTL-4 levels and those of IL-1β, TNF-α, and NFκB in tumor, along with an association between ANGPTL-4 levels with IL-1β and MCP-1 levels in tumor; and ANGPTL-4 and IL-1β levels in MES.MethodsWe studied 102 patients, who were divided into three groups: control patients (C, n=37), cancer patients with a stable weight (WSC, n=23), and cancer-cachexia patients (CC, n=42). Samples of plasma, tumor, mesenteric (MES) and subcutaneous adipose tissue were removed for the determination of ANGPTL-4 levels and other proinflammatory factors.ConclusionsANGPTL-4 levels were higher in plasma and tumor of CC-group, and positively associated with pro-inflammatory and pro-tumorigenic factors. Our results suggest an opposite effect of ANGPTL-4 depending on the concentration and presence of cachexia.
Highlights
Cancer cachexia is a systemic disease affecting the vast majority of patients with end stage cancer, contributing to poor quality of life and decreased life expectancy [1, 2]
In weight-stable cancer patient (WSC), we identified an association between the plasmatic ANGPTL-4, IL-15, and IL-10 in tumor and IL-15 in MES
Taken all together our results suggest that increased ANGPTL-4 levels may contribute for a proinflammatory environment on cancer cachexia patients
Summary
Cancer cachexia is a systemic disease affecting the vast majority of patients with end stage cancer, contributing to poor quality of life and decreased life expectancy [1, 2]. In cancer-cachexia, adipose tissue suffers excessive lipolysis, decreased lipogenesis de novo and uptake of fatty acids from triacylglycerol from lipoproteins by a reduction on activity of lipoprotein lipase [3]. All these metabolic alterations contribute to adipose tissue wasting. It has been reported that, in cancer cachexia, white adipose cells suffering ‘browning’ increase heat production and energy expenditure. Conclusions: ANGPTL-4 levels were higher in plasma and tumor of CC-group, and positively associated with pro-inflammatory and pro-tumorigenic factors. Our results suggest an opposite effect of ANGPTL-4 depending on the concentration and presence of cachexia
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