| RRC ID |
12694
|
| 著者 |
Murata T, Aritake K, Matsumoto S, Kamauchi S, Nakagawa T, Hori M, Momotani E, Urade Y, Ozaki H.
|
| タイトル |
Prostagladin D2 is a mast cell-derived antiangiogenic factor in lung carcinoma.
|
| ジャーナル |
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.
|
| 巻・号 |
108(49)
|
| ページ |
19802-7
|
| 公開日 |
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
|
| 引用数 |
35
|
|
WOS 分野
|
MULTIDISCIPLINARY SCIENCES
|
| リソース情報 |
| 実験動物マウス |
RBRC01888 |
