Arner Erik, Forrest Alistair R R, Ehrlund Anna, Mejhert Niklas, Itoh Masayoshi, Kawaji Hideya, Lassmann Timo, Laurencikiene Jurga, Rydén Mikael, Arner Peter
RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Kanagawa, Japan; Department of Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Huddinge, Sweden; RIKEN Omics Science Center, Yokohama, Kanagawa, Japan.
RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Kanagawa, Japan; RIKEN Omics Science Center, Yokohama, Kanagawa, Japan.
PLoS One. 2014 Mar 27;9(3):e80274. doi: 10.1371/journal.pone.0080274. eCollection 2014.
Obesity confers an increased risk of developing specific cancer forms. Although the mechanisms are unclear, increased fat cell secretion of specific proteins (adipokines) may promote/facilitate development of malignant tumors in obesity via cross-talk between adipose tissue(s) and the tissues prone to develop cancer among obese. We searched for novel adipokines that were overexpressed in adipose tissue of obese subjects as well as in tumor cells derived from cancers commonly associated with obesity. For this purpose expression data from human adipose tissue of obese and non-obese as well as from a large panel of human cancer cell lines and corresponding primary cells and tissues were explored. We found expression of ceruloplasmin to be the most enriched in obesity-associated cancer cells. This gene was also significantly up-regulated in adipose tissue of obese subjects. Ceruloplasmin is the body's main copper carrier and is involved in angiogenesis. We demonstrate that ceruloplasmin is a novel adipokine, which is produced and secreted at increased rates in obesity. In the obese state, adipose tissue contributed markedly (up to 22%) to the total circulating protein level. In summary, we have through bioinformatic screening identified ceruloplasmin as a novel adipokine with increased expression in adipose tissue of obese subjects as well as in cells from obesity-associated cancers. Whether there is a causal relationship between adipose overexpression of ceruloplasmin and cancer development in obesity cannot be answered by these cross-sectional comparisons.
肥胖会增加患特定癌症的风险。尽管其机制尚不清楚,但脂肪细胞分泌的特定蛋白质(脂肪因子)增加可能通过脂肪组织与肥胖人群中易患癌症的组织之间的相互作用,促进肥胖人群中恶性肿瘤的发展。我们在肥胖受试者的脂肪组织以及源自与肥胖相关的常见癌症的肿瘤细胞中寻找过表达的新型脂肪因子。为此,我们研究了来自肥胖和非肥胖人群的人类脂肪组织以及大量人类癌细胞系、相应原代细胞和组织的表达数据。我们发现铜蓝蛋白在与肥胖相关的癌细胞中表达最为丰富。该基因在肥胖受试者的脂肪组织中也显著上调。铜蓝蛋白是人体主要的铜载体,参与血管生成。我们证明铜蓝蛋白是一种新型脂肪因子,在肥胖状态下其产生和分泌速率增加。在肥胖状态下,脂肪组织对循环总蛋白水平的贡献显著(高达22%)。总之,我们通过生物信息学筛选确定铜蓝蛋白是一种新型脂肪因子,在肥胖受试者的脂肪组织以及与肥胖相关癌症的细胞中表达增加。这些横断面比较无法回答铜蓝蛋白在脂肪组织中的过表达与肥胖相关癌症发展之间是否存在因果关系。