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They have abnormal characteristics compared to the ECs in normal tissues. Here, we found a marked increase in lipocalin\u2010type prostaglandin D synthase (L\u2010PGDS) mRNA (<jats:italic>Ptgds<\/jats:italic>) expression in ECs isolated from mouse melanoma. Immunostaining of mouse melanoma revealed expression of L\u2010PGDS protein in the ECs. <jats:italic>In situ<\/jats:italic> hybridization also showed L\u2010PGDS (PTGDS) mRNA expression in the ECs of human melanoma and oral squamous cell carcinoma. <jats:italic>In vitro<\/jats:italic> experiments showed that stimulation with tumor cell\u2010derived IL\u20101 and TNF\u2010\u03b1 increased L\u2010PGDS mRNA expression and its product prostaglandin D<jats:sub>2<\/jats:sub> (PGD<jats:sub>2<\/jats:sub>) in human normal ECs. We also investigated the contribution of L\u2010PGDS\u2013PGD<jats:sub>2<\/jats:sub> to tumor growth and vascularization. Systemic or EC\u2010specific deficiency of L\u2010PGDS accelerated the growth of melanoma in mice, whereas treatment with an agonist of the PGD<jats:sub>2<\/jats:sub> receptor, DP1 (BW245C, 0.1\u2009mg\/kg, injected intraperitoneally twice daily), attenuated it. Morphological and <jats:italic>in vivo<\/jats:italic> studies showed that endothelial L\u2010PGDS deficiency resulted in functional changes of tumor ECs such as accelerated vascular hyperpermeability, angiogenesis, and endothelial\u2010to\u2010mesenchymal transition (EndMT) in tumors, which in turn reduced tumor cell apoptosis. These observations suggest that tumor cell\u2010derived inflammatory cytokines increase L\u2010PGDS expression and subsequent PGD<jats:sub>2<\/jats:sub> production in the tumor ECs. This PGD<jats:sub>2<\/jats:sub> acts as a negative regulator of the tumorigenic changes in tumor ECs. Copyright \u00a9 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4993","type":"journal-article","created":{"date-parts":[[2017,11,10]],"date-time":"2017-11-10T00:02:43Z","timestamp":1510272163000},"page":"84-96","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Lipocalin\u2010type prostaglandin D synthase\u2010derived PGD<sub>2<\/sub> attenuates malignant properties of tumor endothelial cells"],"prefix":"10.1002","volume":"244","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0159-9994","authenticated-orcid":false,"given":"Keisuke","family":"Omori","sequence":"first","affiliation":[{"name":"Department of Animal Radiology, Graduate School of Agriculture and Life Sciences The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teppei","family":"Morikawa","sequence":"additional","affiliation":[{"name":"Department of Pathology, Graduate School of Medicine The 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