Neto Nelson Inácio Pinto, Boldarine Valter Tadeu, Hachul Ana Claudia Losinskas, Oyama Lila Missae, Lima Joanna Darck Carola Correia, Fernandez Estefania Simoes, Otoch José Pinhata, de Alcântara Paulo Sérgio Martins, Tokeshi Flavio, Seelaender Marilia Cerqueira Leite, Oller do Nascimento Claudia Maria da Penha
Departamento de Fisiologia, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, Brazil.
Institute of Biomedical Sciences, Cancer Metabolism Research Group, University of São Paulo, São Paulo, Brazil.
Oncotarget. 2019 Nov 5;10(60):6444-6455. doi: 10.18632/oncotarget.27269.
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.
血管生成素样4（ANGPTL-4）在血管生成和炎症信号传导中具有重要作用，但其在癌症恶病质和炎症发展中的作用报道结果相互矛盾。我们的目的是分析体重稳定的结直肠癌患者和恶病质患者的ANGPTL-4水平，以建立ANGPTL-4与炎症过程之间的关系。
与其他组相比，癌症恶病质（CC）组的血浆和肿瘤ANGPTL-4水平更高。在CC组肿瘤中，血浆ANGPTL-4与NFκB水平之间存在正相关。在体重稳定的癌症患者（WSC）中，我们发现血浆ANGPTL-4、肿瘤中的IL-15和IL-10以及肠系膜（MES）中的IL-15之间存在关联。与WSC组相比，CC组MES中NFκB和TNF-R1水平升高。特别是在CC组中，肿瘤中ANGPTL-4水平与IL-1β、TNF-α和NFκB水平之间存在正相关，同时肿瘤中ANGPTL-4水平与IL-1β和MCP-1水平之间存在关联；以及MES中ANGPTL-4和IL-1β水平之间存在关联。
我们研究了102例患者，分为三组：对照组患者（C，n = 37）、体重稳定的癌症患者（WSC，n = 23）和癌症恶病质患者（CC，n = 42）。采集血浆、肿瘤、肠系膜（MES）和皮下脂肪组织样本，用于测定ANGPTL-4水平和其他促炎因子。
CC组的血浆和肿瘤中ANGPTL-4水平较高，且与促炎和促肿瘤因子呈正相关。我们的结果表明，ANGPTL-4的作用取决于恶病质的浓度和存在情况，呈现相反的效应。
