title: Lipocalin2 as a plasma marker for tumors with hypoxic regions.
abstract: Hypoxic tumors have been identified as appropriate indicators of tumor malignancy. However, no convenient plasma marker for hypoxic tumors has been described. Therefore, to identify a novel, convenient plasma marker for hypoxic tumors, we used microarray analysis to compare gene expression profiles of normoxic and hypoxic tumor tissues of mice bearing melanomas. Among the upregulated genes detected in hypoxic tumors, we chose to study the secretory protein lipocalin2 (LCN2) as a marker for hypoxic tumors. LCN2 protein levels in the plasma of mice bearing hypoxic tumors were significantly increased compared with those in mice bearing normoxic tumors. Interestingly, LCN2 mRNA levels were 17-fold higher in HIF-1α-positive hypoxic tumors than in HIF-1α-negative normoxic tumors. Furthermore, LCN2 mRNA levels were significantly higher in the B16-F1 cells and various human tumor cells cultured under hypoxic conditions than in cells cultured under normoxic conditions, while no changes in mRNA expression were observed in nontumor NIH-3T3 cells, even under hypoxic conditions. In cultured cells, the expression pattern of LCN2 was mostly consistent with that of HIF-1α, whereas that of a conventional hypoxic marker, carbonic anhydrase IX, was not. Collectively, our data suggested that LCN2 was a useful plasma marker for hypoxic tumors.
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Ibuki
authors.initials: I
authors.lastname: Nakamura
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Hama
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Itakura
authors.affiliation: Division of Molecular Genetics Research, Life Science Research Center, University of Toyama, Toyama, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takasaki
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nishi
authors.affiliation: Division of Molecular Genetics Research, Life Science Research Center, University of Toyama, Toyama, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tabuchi
authors.affiliation: Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kogure
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D056945:Hep G2 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood* / Q000378:metabolism; D061986:MCF-7 Cells; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D015513:Oncogene Proteins / Q000097:blood* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000209:Acute-Phase Proteins; D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C071332:Lcn2 protein, mouse