Ceruloplasmin Is a Novel Adipokine Which Is Overexpressed in Adipose Tissue of Obese Subjects and in Obesity-Associated Cancer Cells

• Published in: PloS one Vol. 9; no. 3; p. e80274
• Main Authors: Arner, Erik, Forrest, Alistair R. R., Ehrlund, Anna, Mejhert, Niklas, Itoh, Masayoshi, Kawaji, Hideya, Lassmann, Timo, Laurencikiene, Jurga, Rydén, Mikael, Arner, Peter
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.03.2014; Public Library of Science (PLoS)
• Subjects: Adipocytes; Adipocytes - metabolism; Adipokines - genetics; Adipokines - metabolism; Adipose tissue; Adipose Tissue - metabolism; Adult; Analysis; Angiogenesis; Biology and Life Sciences; Body fat; Body mass index; Cancer; Cancer cells; Case-Control Studies; Cell Line, Tumor; Ceruloplasmin; Ceruloplasmin - genetics; Ceruloplasmin - metabolism; Committees; Computational Biology - methods; Computer and Information Sciences; Consortia; Copper; Databases, Genetic; Development and progression; Diabetes; Ethics; Female; Gastrointestinal surgery; Gene Expression; Gene Expression Profiling; Genes; Genetic Loci; Genomics - methods; Health aspects; Health care; Health risks; Humans; Kidney cancer; Life sciences; Male; Medicine and Health Sciences; Middle Aged; Neoplasms - etiology; Obesity; Obesity - complications; Obesity - genetics; Preventive medicine; Proteins; Secretion; Sweden; Tissues; Tumor cell lines; Tumor cells; Tumors; Type 2 diabetes; Sweden; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0080274

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.