title: Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: Erik
authors.initials: E
authors.lastname: Arner
authors.affiliation: RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Kanagawa, Japan; RIKEN Omics Science Center, Yokohama, Kanagawa, Japan.
authors.forename: Alistair R R
authors.initials: AR
authors.lastname: Forrest
authors.affiliation: Department of Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Huddinge, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Ehrlund
authors.affiliation: Department of Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Huddinge, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Mejhert
authors.affiliation: RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Kanagawa, Japan; RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan; RIKEN Omics Science Center, Yokohama, Kanagawa, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Itoh
authors.affiliation: RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Kanagawa, Japan; RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan; RIKEN Omics Science Center, Yokohama, Kanagawa, Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Kawaji
authors.affiliation: RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Kanagawa, Japan; RIKEN Omics Science Center, Yokohama, Kanagawa, Japan.
authors.forename: Timo
authors.initials: T
authors.lastname: Lassmann
authors.affiliation: Department of Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Huddinge, Sweden.
authors.forename: Jurga
authors.initials: J
authors.lastname: Laurencikiene
authors.affiliation: Department of Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Huddinge, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Rydén
authors.affiliation: Department of Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Huddinge, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D054392:Adipokines / Q000235:genetics* / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002570:Ceruloplasmin / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D056426:Genetic Loci; D023281:Genomics / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology*; D009765:Obesity / Q000150:complications* / Q000235:genetics*; D013548:Sweden
chemical_list: D054392:Adipokines; D002570:Ceruloplasmin