Role of thymidine phosphorylase on invasive potential in lung adenocarcinoma
| Project/Area Number |
17590779
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | National Cardiovascular Center Research Institute (2006)
Yamagata University (2005) |
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Principal Investigator |
SATA Makoto National Cardiovascular Center, Department of Internal Medicine, Physician-in-Chief, 臨床検査部細菌免疫検査室, 医長 (00280892)
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| Co-Investigator(Kenkyū-buntansha) |
柴田 陽光 山形大学, 医学部, 助手 (60333978)
高畠 典明 山形大学, 医学部, 助手 (80344795)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | thymidine phosphorylase / lung cancer / clarithromycin / invasion / lung adenocarcinoma / metastasis / integrin / clearthromycin |
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| Research Abstract |
Thymidine phosphorylase (TP) is expressed at higher levels in a variety of human cancers than in adjacent normal tissue. It is reported that the higher expression is associated with an increase of intratumoral microvessel density and a poor prognosis. We investigated the role of TP in human non-small cell lung cancers (NSCLC). The concentrations of TP in the tumors and the adjacent normal tissue from surgically resected specimens of 54 cases of NSCLC were measured by using an enzyme-linked immunosorbent assay. Tumor specimens were also examined immunohistochemically. TP concentrations in the tumors were 169 ± 18 Unit/mg protein (mean ± SD), whereas those in normal tissue were 43 ± 4 Unit/mg protein (mean ± SD) consistent with TP staining patterns. There was no correlation between TP expression and microvessel density. Among clinicopathological factors examined, the concentrations of TP but not TP immunoreactivity correlated with tumor differentiation in lung adenocarcinoma. Although a
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specific TP inhibitor (TPI) and overexpression of TP did not affect the growth of A549 lung adenocarcinoma cells, Matrigel invasion assay showed that A549 transfected with TP had higher invasive potential than mock transfectant and such enhanced invasive activity was dramatically diminished by treatment with TPI. Furthermore, administration of TPI suppressed lung metastasis of TP-overexpressing A549 cells in nude mice. These results demonstrate that TP may play an important role in tumor differentiation, invasiveness, and metastasis in lung adenocarcinoma and suggest that TP could be a novel target for treatment of TP-overexpressing lung adenocarcinoma.
It has been speculated that clarithromycin (CAM), a 14-membered ring macrolide, has an antitumor effect besides antimicrobial and anti-inflammatory effects. We evaluated the effects of CAM on growth and invasiveness of A549 lung adenocarcinoma cells. Although CAM did not affect the growth of A549 cells, Matrigel invasion assay showed that the potential of invasion was diminished by CAM treatment. When analyzed by flow cytometry, CAM suppressed integrin α2 and β1 expression. Furthermore, thymidine phosphorylase (TP) expression was diminished by CAM treatment in a dose-dependent manner. A specific TP inhibitor also suppressed expression of β1. integrin in flow cytometry analysis. These results suggest that CAM may suppress invasive activity of A549 cells in part by diminishing the expression of TP, integrin α2, and integrin β1, which may be a downstream signal of TP pathway, and that CAM could be useful for the treatment of lung adenocarcinoma. Less
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Report
(3 results)
Research Products
(26 results)
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[Journal Article] Clarithromycin suppresses invasiveness of human lung adenocarcinoma cells.2007
Author(s)
Wada T, Sata M, Sato J, Tokairin Y, Machiya J, Hirama N, Arao T, Inoue S, Takabatake N, Shibata Y, Kubota I
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Journal Title
Chemotherapy 53
Pages: 77-84
Description
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[Journal Article] Intronic single-nucleotide polymorphisms in Bcl-2 are associated with chronic obstructive pulmonary disease severity.2007
Author(s)
Sata M, Takabatake N, Inoue S, Shibata Y, Abe S, Machiya J, Wada T, Ji G, Kido T, Matsuura T, Muramatsu M, Kubota I
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Journal Title
Respirology 12
Pages: 34-41
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[Journal Article] Treatment and transfer of emphysema by a new bone marrow transplantation method from normal mice to Tsk mice and vice versa.2006
Author(s)
Adachi Y, Oyaizu H, Taketani S, Minamino K, Yamaguchi K, Shultz LD, Iwasaki M, Tomita M, Suzuki Y, Nakano K, Koike Y, Yasumizu R, Sata M, Hirama N, Kubota I, Fukuhara S, Ikehara S
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Stem Cells 24
Pages: 2071-2077
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[Journal Article] A single polymorphism in CCL1 gene predicts acute exacerbations in COPD.2006
Author(s)
Takabatake N, Shibata Y, Abe S, Wada T, Machiya J, Igarashi A, Tokairin Y, Ji G, Sato H, Sata M, Takeishi Y, Emi M, Muramatsu M, Kubota I
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Journal Title
Am J Respir Crit Care Med 174
Pages: 875-885
Description
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[Journal Article] Involvement of pulmonary endothelial cell injury in the pathogenesis of pulmonary fibrosis : clinical assessment by ^<123>I-MIBG lung scintigraphy.2005
Author(s)
Takabatake N, Arao T, Sata M, Abe S, Inoue S, Shibata Y, Honma T, Takahashi K, Okada A, Takeishi Y, Kubota I
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Journal Title
Eur J Nucl Med Mol Imaging 32
Pages: 221-228
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[Journal Article] Expression and Localization of Diacylglycerol Kinase Isozymes and Enzymatic Features in Rat Lung.2005
Author(s)
Katagiri Y, Ito T, Saino-Saito S, Hozumi Y, Suwabe A, Otake K, Sata M, Kondo H, Sakane F, Kanoh H, Kubota I, Goto K
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Journal Title
Am J Physiol Lung Cell Mol Physiol 288
Description
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[Journal Article] A novel polymorphism in secretory phospholipase A_2-IID is : associated with body weight loss in COPD.2005
Author(s)
Takabatake N, Sata M, Inoue S, Shibata Y, Abe S, Wada T, Machiya J, Ji G, Matsuura T, Takeishi Y, Muramatsu M, Kubota I
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Journal Title
Am J Respir Crit Care Med 172 (Originally published in press as DOI:10.1164/rccm.200503-3190C on July 7 2005)
Pages: 1097-1104
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