Association between ANGPTL-4 and the proinflammatory process in cancer cachexia patients
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Nelson Inácio Pinto Neto1, Valter Tadeu Boldarine1, Ana Claudia Losinskas Hachul1, Lila Missae Oyama1, Joanna Darck Carola Correia Lima3, Estefania Simoes Fernandez3, José Pinhata Otoch2, Paulo Sérgio Martins de Alcântara2, Flavio Tokeshi2, Marilia Cerqueira Leite Seelaender2,3 and Claudia Maria da Penha Oller do Nascimento1
1 Departamento de Fisiologia, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, Brazil
2 Department of Clinical Surgery, University of São Paulo, São Paulo, Brazil
3 Institute of Biomedical Sciences, Cancer Metabolism Research Group, University of São Paulo, São Paulo, Brazil
|Nelson Inácio Pinto Neto,||email:||[email protected]|
Keywords: ANGPTL-4; cytokines; tumor; cachexia; proinflammatory process
Received: May 20, 2019 Accepted: September 24, 2019 Published: November 5, 2019
Contradictory 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.
Plasma 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.
We 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.
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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