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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Nakagawa, Takayuki Momotani, Eiichi Hori, Masatoshi Ozaki, Hiroshi Murata, Takahisa Matsumoto, Shigeko Kamauchi, Shinya Urade, Yoshihiro Aritake, Kosuke |
| Description | Author Affiliation: Murata T ( Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan. amurata@mail.ecc.u-tokyo.ac.jp); |
| Abstract | It is well established that prostaglandins (PGs) are involved in tumor angiogenesis and growth, yet the role of prostaglandin D(2) (PGD(2)) remains virtually unknown. Here, we show that host hematopoietic PGD(2) synthase (H-PGDS) deficiency enhances Lewis lung carcinoma (LLC) progression, accompanied by increased vascular leakage, angiogenesis, and monocyte/mast cell infiltration. This deficiency can be rescued by hematopoietic reconstitution with bone marrow from H-PGDS-naive (WT) mice. In tumors on WT mice, c-kit(+) mast cells highly express H-PGDS. Host H-PGDS deficiency markedly up-regulated the expression of proangiogenic factors, including TNF- in the tumor. In mast cell-null Kit(W-sh/W-sh) mice, adoptive transfer of H-PGDS-deficient mast cells causes stronger acceleration in tumor angiogenesis and growth than in WT mast cells. In response to LLC growth, H-PGDS-deficient mast cells produce TNF- excessively. This response is suppressed by the administration of a synthetic PGD(2) receptor agonist or a degradation product of PGD(2), 15-deoxy-Δ(12,14)-PGJ(2). Additional TNF- deficiency partially counteracts the tumorigenic properties seen in H-PGDS-deficient mast cells. These observations identify PGD(2) as a mast cell-derived antiangiogenic factor in expanding solid tumors. Mast cell-derived PGD(2) governs the tumor microenvironment by restricting excessive responses to vascular permeability and TNF- production. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 49 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Carcinoma, Lewis Lung Metabolism Mast Cells Neovascularization, Pathologic Prostaglandin D2 Animals Apoptosis Drug Effects Bone Marrow Cells Genetics Pathology Cell Line, Tumor Cells, Cultured Flow Cytometry Immunohistochemistry Intramolecular Oxidoreductases Deficiency Lipocalins Mice Mice, Inbred C57BL Mice, Knockout Analogs & Derivatives Pharmacology Receptors, Immunologic Antagonists & Inhibitors Receptors, Prostaglandin Time Factors Tumor Necrosis Factor-alpha Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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