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dc.contributor.authorTunçer, S.en_US
dc.contributor.authorKeşküş, A. G.en_US
dc.contributor.authorÇolakoğlu, M.en_US
dc.contributor.authorÇimen, I.en_US
dc.contributor.authorYener, C.en_US
dc.contributor.authorKonu, Ö.en_US
dc.contributor.authorBanerjee, S.en_US
dc.date.accessioned2018-04-12T11:13:04Z
dc.date.available2018-04-12T11:13:04Z
dc.date.issued2017-11en_US
dc.identifier.issn0898-6568
dc.identifier.urihttp://hdl.handle.net/11693/37424
dc.description.abstract15-lipoxygenase-1 (15-LOX-1) oxygenates linoleic acid to 13(S)-hydroxyoctadecadienoic acid (HODE). The enzyme is widely suppressed in different cancers and its re-expression has tumor suppressive effects. 15-LOX-1 has been shown to inhibit neoangiogenesis in colorectal cancer (CRC); in the present study we confirm this phenomenon and describe the mechanistic basis. We show that re-expression of 15-LOX-1 in CRC cell lines resulted in decreased transcriptional activity of HIF1α and reduced the expression and secretion of VEGF in both normoxic and hypoxic conditions. Conditioned medium (CM) was obtained from CRC or prostate cancer cell lines re-expressing 15-LOX-1 (15-LOX-1CM). 15-LOX-1CM treated aortic rings from 6-week old C57BL/6 mice showed significantly less vessel sprouting and more organized structure of vascular network. Human umbilical vein endothelial cells (HUVECs) incubated with 15-LOX-1CM showed reduced motility, enhanced expression of intercellular cell adhesion molecule (ICAM-1) and reduced tube formation but no change in proliferation or cell-cycle distribution. HUVECs incubated with 13(S)-HODE partially phenocopied the effects of 15-LOX-1CM, i.e., showed reduced motility and enhanced expression of ICAM-1, but did not reduce tube formation, implying the importance of additional factors. Therefore, a Proteome Profiler Angiogenesis Array was carried out, which showed that Thrombospondin-1 (TSP-1), a matrix glycoprotein known to strongly inhibit neovascularization, was expressed significantly more in HUVECs incubated with 15-LOX-1CM. TSP-1 blockage in HUVECs reduced the expression of ICAM-1 and enhanced cell motility, thereby providing a mechanism for reduced angiogenesis. The anti-angiogenic effects of 15-LOX-1 through enhanced expressions of ICAM-1 and TSP-1 are novel findings and should be explored further to develop therapeutic options.en_US
dc.language.isoEnglishen_US
dc.source.titleCellular Signallingen_US
dc.relation.isversionofhttps://doi.org/10.1016/j.cellsig.2017.07.022en_US
dc.subject15-LOX-1en_US
dc.subjectAngiogenesisen_US
dc.subjectColorectal canceren_US
dc.subjectICAM-1en_US
dc.subjectThrombospondin-1en_US
dc.subject13 hydroxyoctadecadienoic aciden_US
dc.subject15 lipoxygenase 1en_US
dc.subjectArachidonate 15 lipoxygenaseen_US
dc.subjectHypoxia inducible factor 1alphaen_US
dc.subjectIntercellular adhesion molecule 1en_US
dc.subjectPolyunsaturated fatty aciden_US
dc.subjectThrombospondin 1en_US
dc.subjectUnclassified drugen_US
dc.subjectAnimal tissueen_US
dc.subjectAortic ring (slice)en_US
dc.subjectArticleen_US
dc.subjectCell cycleen_US
dc.subjectCell motilityen_US
dc.subjectCell proliferationen_US
dc.subjectColorectal canceren_US
dc.subjectControlled studyen_US
dc.subjectEx vivo studyen_US
dc.subjectHumanen_US
dc.subjectHuman cellen_US
dc.subjectLNCaP cell lineen_US
dc.subjectMaleen_US
dc.subjectMouseen_US
dc.subjectNonhumanen_US
dc.subjectPriority journalen_US
dc.subjectProstate cancer cell lineen_US
dc.subjectProtein expressionen_US
dc.subjectSignal transductionen_US
dc.subjectTranscription regulationen_US
dc.subjectTumor vascularizationen_US
dc.subjectUmbilical vein endothelial cellen_US
dc.title15-Lipoxygenase-1 re-expression in colorectal cancer alters endothelial cell features through enhanced expression of TSP-1 and ICAM-1en_US
dc.typeArticleen_US
dc.departmentDepartment of Molecular Biology and Genetics
dc.citation.spage44en_US
dc.citation.epage54en_US
dc.citation.volumeNumber39en_US
dc.identifier.doi10.1016/j.cellsig.2017.07.022en_US
dc.publisherElsevieren_US


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