論文 - 詳細
| RRC ID | 52464 |
|---|---|
| 著者 | Omori K, Morikawa T, Kunita A, Nakamura T, Aritake K, Urade Y, Fukayama M, Murata T. |
| タイトル | Lipocalin-type prostaglandin D synthase-derived PGD2 attenuates malignant properties of tumor endothelial cells. |
| ジャーナル | J Pathol |
| Abstract |
Endothelial cells (ECs) are a key component of the tumor microenvironment. They have abnormal characteristics compared to the ECs in normal tissues. Here, we found a marked increase in lipocalin-type prostaglandin D synthase (L-PGDS) mRNA (Ptgds) expression in ECs isolated from mouse melanoma. Immunostaining of mouse melanoma revealed expression of L-PGDS protein in the ECs. In situ hybridization also showed L-PGDS (PTGDS) mRNA expression in the ECs of human melanoma and oral squamous cell carcinoma. In vitro experiments showed that stimulation with tumor cell-derived IL-1 and TNF-α increased L-PGDS mRNA expression and its product prostaglandin D2 (PGD2 ) in human normal ECs. We also investigated the contribution of L-PGDS-PGD2 to tumor growth and vascularization. Systemic or EC-specific deficiency of L-PGDS accelerated the growth of melanoma in mice, whereas treatment with an agonist of the PGD2 receptor, DP1 (BW245C, 0.1 mg/kg, injected intraperitoneally twice daily), attenuated it. Morphological and in vivo studies showed that endothelial L-PGDS deficiency resulted in functional changes of tumor ECs such as accelerated vascular hyperpermeability, angiogenesis, and endothelial-to-mesenchymal transition (EndMT) in tumors, which in turn reduced tumor cell apoptosis. These observations suggest that tumor cell-derived inflammatory cytokines increase L-PGDS expression and subsequent PGD2 production in the tumor ECs. This PGD2 acts as a negative regulator of the tumorigenic changes in tumor ECs. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| 巻・号 | 244(1) |
| ページ | 84-96 |
| 公開日 | 2018-1-1 |
| DOI | 10.1002/path.4993 |
| PMID | 29124765 |
| MeSH | Angiogenesis Inhibitors / metabolism* Animals Apoptosis Capillary Permeability Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology* Cell Line, Tumor Cell Transformation, Neoplastic Corneal Neovascularization Cytokines / metabolism Endothelial Cells / metabolism Epithelial-Mesenchymal Transition Female Humans Intramolecular Oxidoreductases / genetics* Lipocalins / genetics* Melanoma / metabolism Melanoma / pathology* Mice Mice, Inbred C57BL Neoplasms / prevention & control* Prostaglandin D2 / metabolism* Receptors, Immunologic / antagonists & inhibitors Receptors, Prostaglandin / antagonists & inhibitors Tumor Microenvironment |
| IF | 5.942 |
| 引用数 | 13 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | LLC(RCB0558) |