Role of prostaglandin receptor signaling inenhancement of lymphangiogenesis and application to metastasis treatment
Project/Area Number |
23790302
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
General pharmacology
|
Research Institution | Kitasato University |
Principal Investigator |
|
Project Period (FY) |
2011 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | リンパ管新生 / プロスタグランジン / 慢性炎症 / ノックアウトマウス / がん / リンパ節転移 |
Research Abstract |
Lymphangiogesis, the formation of lymphatic vessels from pre-existing lymphatic vessels, plays an important role in homeostasis, metabolism and immunity. Recent evidenceindicates that lymphangiogenesis, similar to angiogenesis, also occurs during certain inflammatory and autoimmune conditions. I examined the effects of COX-2 and endogenous PGE2on lymphangiogenesis during chronic inflammation. Lymphangiogenesis was upregulated during the development of granulation tissues, which were formed around Matrigel plugs in response to inductions of COX-2 and mPGES-1. Administration of a COX-2 inhibitor (celecoxib) significantly reduced lymphatic vessel formation in granulationtissues, whereas topical PGE2administration enhanced lymphangiogenesis.Lymphangiogenesis was suppressed in the granulation tissues of mice lacking either EP3 or EP4, suggesting that these molecules are receptors for PGE2. An EP3-selective agonist (ONO-AE-248) increased the expression of VEGF-C and VEGF-D in cultured macrophages, while an EP4-selective agonist (ONO-AE1-329) increased VEGF-C expression in cultured macrophages and increased VEGF-D expression in cultured fibroblasts. Thus, our findings demonstrate that EP3 and EP4 signaling contributes to inflammation-associated lymphangiogenesis by upregulating VEGF-C and VEGF-D in fibroblasts and macrophages. In addition, prostaglandin receptor signaling appears critical for tumorassociated lymphangiogenesis and tumor growth. From now on, I would like to continue an examinationbased on these findings about the metastasis in lymph node.
|
Report
(3 results)
Research Products
(18 results)
-
[Journal Article] NSAID, aspirin delays gastric ulcer healing with reduced accumulation of CXCR4+ VEGFR1+ cells to theulcer granulation tissues.2013
Author(s)
Sato T, Amano H, Ito Y, Eshima K, Minamino T, Ae T, Katada C, Ohno T, Hosono K, Suzuki T, Shibuya M, Koizumi W, Majima M.
-
Journal Title
Biomed Pharmacother.
Volume: in press
Related Report
Peer Reviewed
-
[Journal Article] Leukotriene B4 type-1 receptor signaling promotes liver repair after hepatic ischemia/reperfusion injury through the enhancement of macrophage recruitment.2013
Author(s)
Ohkubo H, Ito Y, Minamino T, Mishima T, Hirata M, Hosono K, Shibuya M, Yokomizo T, Shimizu T, Watanabe M, Majima M.
-
Journal Title
FASEB J.
Volume: in press
Related Report
Peer Reviewed
-
[Journal Article] Thromboxane A(2) receptor signaling promotes liver tissue repair after toxic injury through the enhancement of macrophage recruitment.2012
Author(s)
Minamino T, Ito Y, Ohkubo H, Hosono K, Suzuki T, Sato T, Ae T, Shibuya A, Sakagami H, Narumiya S, Koizumi W, Majima M.
-
Journal Title
Toxicol Appl Pharmacol.
Volume: 259(1)
Pages: 104-114
Related Report
Peer Reviewed
-
-
-
-
[Journal Article] Calcitonin gene-related peptide facilitates revascularization during hindlimb ischemia in mice.2011
Author(s)
Mishima T, Ito Y, Hosono K, Tamura Y, Uchida Y, Hirata M, Suzsuki T, Amano H, Kato S, Kurihara Y, Kurihara H, Hayashi I, Watanabe M, Majima M.
-
Journal Title
Am J Physiol Heart Circ Physiol.
Volume: 300(2)
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-