Reference - Detail
| RRC ID | 12694 |
|---|---|
| Author | Murata T, Aritake K, Matsumoto S, Kamauchi S, Nakagawa T, Hori M, Momotani E, Urade Y, Ozaki H. |
| Title | Prostagladin D2 is a mast cell-derived antiangiogenic factor in lung carcinoma. |
| Journal | Proc Natl Acad Sci U S A |
| 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-α 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-α 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-α 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-α production. |
| Volume | 108(49) |
| Pages | 19802-7 |
| Published | 2011-12-6 |
| DOI | 10.1073/pnas.1110011108 |
| PII | 1110011108 |
| PMID | 22106279 |
| PMC | PMC3241753 |
| MeSH | Animals Apoptosis / drug effects Bone Marrow Cells / drug effects Bone Marrow Cells / metabolism Carcinoma, Lewis Lung / genetics Carcinoma, Lewis Lung / metabolism* Carcinoma, Lewis Lung / pathology Cell Line, Tumor Cells, Cultured Female Flow Cytometry Immunohistochemistry Intramolecular Oxidoreductases / deficiency Intramolecular Oxidoreductases / genetics Intramolecular Oxidoreductases / metabolism Lipocalins / genetics Lipocalins / metabolism Male Mast Cells / drug effects Mast Cells / metabolism* Mice Mice, Inbred C57BL Mice, Knockout Neovascularization, Pathologic / genetics Neovascularization, Pathologic / metabolism* Prostaglandin D2 / analogs & derivatives Prostaglandin D2 / metabolism* Prostaglandin D2 / pharmacology Receptors, Immunologic / antagonists & inhibitors Receptors, Immunologic / metabolism Receptors, Prostaglandin / antagonists & inhibitors Receptors, Prostaglandin / metabolism Time Factors Tumor Necrosis Factor-alpha / metabolism |
| IF | 9.412 |
| Times Cited | 35 |
| WOS Category | MULTIDISCIPLINARY SCIENCES |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC01888 |