| RRC ID |
44734
|
| 著者 |
Takagi S, Oh-hara T, Sato S, Gong B, Takami M, Fujita N.
|
| タイトル |
Expression of Aggrus/podoplanin in bladder cancer and its role in pulmonary metastasis.
|
| ジャーナル |
Int J Cancer
|
| Abstract |
Platelet aggregation-inducing factor Aggrus, also known as podoplanin, is associated with tumor malignancy by promoting hematogenous metastasis. Aggrus overexpression has been reported in some tumor tissues including lung, esophagus, head and neck and brain. We here found the frequent upregulation of aggrus mRNA in urinary bladder cancers using cancer tissue panels from various organs. Immunohistochemical analysis confirmed Aggrus protein expression in urinary bladder cancers and suggested a positive correlation between Aggrus expression and metastatic tendency in bladder cancers. Endogenous expression of Aggrus protein on the cell surface was found in the mouse bladder cancer MBT-2 cell line and human bladder cancer SCaBER cell lines. Knockdown of Aggrus expression in MBT-2 cells decreased their ability to induce platelet aggregation and form pulmonary metastasis in syngeneic mouse models. Knockdown of Aggrus expression in the human bladder cancer SCaBER cells also attenuated their ability to induce platelet aggregation and form pulmonary metastasis in mice. Moreover, pulmonary metastasis of SCaBER cells was prevented by prior administration of our generated anti-Aggrus neutralizing monoclonal antibodies by attenuating their retention in lung. These results indicate that Aggrus plays an important role in bladder cancer metastasis. Thus, anti-Aggrus neutralizing antibodies would be useful for the prevention of hematogenous metastasis of Aggrus-positive bladder cancer.
|
| 巻・号 |
134(11)
|
| ページ |
2605-14
|
| 公開日 |
2014-6-1
|
| DOI |
10.1002/ijc.28602
|
| PMID |
24222607
|
| PMC |
PMC4233981
|
| MeSH |
Animals
Antibodies, Monoclonal / pharmacology
Apoptosis*
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Blotting, Western
CHO Cells
Carcinoma, Squamous Cell / genetics
Carcinoma, Squamous Cell / metabolism*
Carcinoma, Squamous Cell / pathology
Carcinoma, Transitional Cell / genetics
Carcinoma, Transitional Cell / metabolism*
Carcinoma, Transitional Cell / pathology
Cell Proliferation
Cricetinae
Cricetulus
Flow Cytometry
Humans
Immunoenzyme Techniques
Lung Neoplasms / genetics
Lung Neoplasms / metabolism*
Lung Neoplasms / secondary
Male
Membrane Glycoproteins / antagonists & inhibitors
Membrane Glycoproteins / genetics
Membrane Glycoproteins / metabolism*
Membrane Proteins / antagonists & inhibitors
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Mice
Mice, Inbred C3H
Mice, Inbred ICR
Platelet Aggregation
RNA, Messenger / genetics
RNA, Small Interfering / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Tissue Array Analysis
Urinary Bladder / metabolism
Urinary Bladder / pathology
Urinary Bladder Neoplasms / genetics
Urinary Bladder Neoplasms / metabolism*
Urinary Bladder Neoplasms / pathology
|
| IF |
5.145
|
| 引用数 |
21
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
T24(RCB2356)
MBT-2(RCB0544) |
