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Angiogenic factor thymidine phosphorylase increases cancer cell invasion activity in patients with gastric adenocarcinoma.

Authors
 Eun Jeong Yu  ;  Young Lee  ;  Sun Young Rha  ;  Tae Soo Kim  ;  Hyun Cheol Chung  ;  Bong Kyeong Oh  ;  Woo Ick Yang  ;  Sung Hoon Noh  ;  Hei-Cheul Jeung 
Citation
 MOLECULAR CANCER RESEARCH, Vol.6(10) : 1554-1566, 2008 
Journal Title
 MOLECULAR CANCER RESEARCH 
ISSN
 1541-7786 
Issue Date
2008
MeSH
Actins/metabolism ; Adenocarcinoma/enzymology* ; Adenocarcinoma/pathology* ; Angiogenesis Inducing Agents/metabolism* ; Cell Adhesion/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Collagen/metabolism ; Deoxyribose/pharmacology ; Drug Combinations ; Drug Synergism ; Enzyme Inhibitors/pharmacology ; Humans ; Laminin/metabolism ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Kinases/metabolism ; Proteoglycans/metabolism ; Recombinant Proteins/pharmacology ; Stomach Neoplasms/enzymology* ; Stomach Neoplasms/pathology* ; TOR Serine-Threonine Kinases ; Thymidine Phosphorylase/antagonists & inhibitors ; Thymidine Phosphorylase/metabolism*
Keywords
Actins/metabolism ; Adenocarcinoma/enzymology* ; Adenocarcinoma/pathology* ; Angiogenesis Inducing Agents/metabolism* ; Cell Adhesion/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Collagen/metabolism ; Deoxyribose/pharmacology ; Drug Combinations ; Drug Synergism ; Enzyme Inhibitors/pharmacology ; Humans ; Laminin/metabolism ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Kinases/metabolism ; Proteoglycans/metabolism ; Recombinant Proteins/pharmacology ; Stomach Neoplasms/enzymology* ; Stomach Neoplasms/pathology* ; TOR Serine-Threonine Kinases ; Thymidine Phosphorylase/antagonists & inhibitors ; Thymidine Phosphorylase/metabolism*
Abstract
We investigated the biological role of thymidine phosphorylase (TP), an angiogenic factor, in gastric cancer cell migration and invasion and explored a therapeutic approach for high TP-expressing tumors using TP enzymatic inhibitor (TPI) and rapamycin. We established TP cDNA overexpressing gastric cancer cell lines (MKN-45/TP and YCC-3/TP) and did invasion and adhesion assays with Matrigel-coated transwell membranes. The related signal pathway using recombinant human TP (rhTP), deoxy-d-ribose (D-dRib), and signal pathway inhibitors (wortmannin, LY294002, and rapamycin) was investigated. First, AGS and MKN-1 gastric cancer cell lines showed dose-dependent up-regulation of invasiveness through Matrigel following treatment with rhTP or D-dRib. TP-overexpressing cancer cell lines displayed increased migration and invasion activity, which doubled with rhTP and D-dRib treatment. This activity depended on the enzymatic activity of TP, and TP stimulated the adhesion of cancer cells onto Matrigel and induced actin filament remodeling. Finally, we showed that this activity is related to increased phosphatidylinositol 3-kinase activity in TP-overexpressing cells and that combination treatment with rapamycin and TP enzymatic inhibitor produces an additive effect to abrogate TP-induced invasion. Taken together, TP increases the migration and invasion of gastric cancer cells, especially in TP-expressing cells. Therapies targeting TP might diminish the propensity for invasion and metastasis in gastric cancer
Files in This Item:
T200801338.pdf Download
DOI
10.1158/1541-7786.MCR-08-0166
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Cancer Metastasis Research Center (암전이연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Noh, Sung Hoon(노성훈) ORCID logo https://orcid.org/0000-0003-4386-6886
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Yang, Woo Ick(양우익) ORCID logo https://orcid.org/0000-0002-6084-5019
Oh, Bong Kyeong(오봉경)
Yu, Eun Jeong(유은정)
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
Jeung, Hei Cheul(정희철) ORCID logo https://orcid.org/0000-0003-0952-3679
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/107641
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