| RRC ID |
44458
|
| 著者 |
Arai K, Sakamoto R, Kubota D, Kondo T.
|
| タイトル |
Proteomic approach toward molecular backgrounds of drug resistance of osteosarcoma cells in spheroid culture system.
|
| ジャーナル |
Proteomics
|
| Abstract |
Chemoresistance is one of the most critical prognostic factors in osteosarcoma, and elucidation of the molecular backgrounds of chemoresistance may lead to better clinical outcomes. Spheroid cells resemble in vivo cells and are considered an in vitro model for the drug discovery. We found that spheroid cells displayed more chemoresistance than conventional monolayer cells across 11 osteosarcoma cell lines. To investigate the molecular mechanisms underlying the resistance to chemotherapy, we examined the proteomic differences between the monolayer and spheroid cells by 2D-DIGE. Of the 4762 protein species observed, we further investigated 435 species with annotated mass spectra in the public proteome database, Genome Medicine Database of Japan Proteomics. Among the 435 protein species, we found that 17 species exhibited expression level differences when the cells formed spheroids in more than five cell lines and four species out of these 17 were associated with spheroid-formation associated resistance to doxorubicin. We confirmed the upregulation of cathepsin D in spheroid cells by western blotting. Cathepsin D has been implicated in chemoresistance of various malignancies but has not previously been implemented in osteosarcoma. Our study suggested that the spheroid system may be a useful tool to reveal the molecular backgrounds of chemoresistance in osteosarcoma.
|
| 巻・号 |
13(15)
|
| ページ |
2351-60
|
| 公開日 |
2013-8-1
|
| DOI |
10.1002/pmic.201300053
|
| PMID |
23712969
|
| MeSH |
Antineoplastic Agents / pharmacology*
Bone Neoplasms / drug therapy*
Bone Neoplasms / metabolism*
Bone Neoplasms / pathology
Cell Line, Tumor
Drug Resistance, Neoplasm
Electrophoresis, Gel, Two-Dimensional
Humans
Osteosarcoma / drug therapy*
Osteosarcoma / metabolism*
Osteosarcoma / pathology
Proteome / analysis
Proteome / metabolism*
Proteomics
Spheroids, Cellular
|
| IF |
3.254
|
| 引用数 |
31
|
|
WOS 分野
|
BIOCHEMICAL RESEARCH METHODS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HS-Os-1(RCB2229)
NOS-1(RCB1032)
NOS-10(RCB2348) |
