Association between ANGPTL-4 and the proinflammatory process in cancer cachexia patients.

// Nelson Inacio Pinto Neto 1 , Valter Tadeu Boldarine 1 , Ana Claudia Losinskas Hachul 1 , Lila Missae Oyama 1 , Joanna Darck Carola Correia Lima 3 , Estefania Simoes Fernandez 3 , Jose Pinhata Otoch 2 , Paulo Sergio Martins de Alcântara 2 , Flavio Tokeshi 2 , Marilia Cerqueira Leite Seelaender 2 , 3 and Claudia Maria da Penha Oller do Nascimento 1 1 Departamento de Fisiologia, Universidade Federal de Sao Paulo, Escola Paulista de Medicina, Sao Paulo, Brazil 2 Department of Clinical Surgery, University of Sao Paulo, Sao Paulo, Brazil 3 Institute of Biomedical Sciences, Cancer Metabolism Research Group, University of Sao Paulo, Sao Paulo, Brazil Correspondence to: Nelson Inacio Pinto Neto, email: nelson_nip@hotmail.com Keywords: ANGPTL-4; cytokines; tumor; cachexia; proinflammatory process Received: May 20, 2019     Accepted: September 24, 2019     Published: PUBLISHED_DATE ABSTRACT Background 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. Results 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. Methods 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. 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.