RRC ID |
47698
|
著者 |
Ando T, Kudo Y, Iizuka S, Tsunematsu T, Umehara H, Shrestha M, Matsuo T, Kubo T, Shimose S, Arihiro K, Ogawa I, Ochi M, Takata T.
|
タイトル |
Ameloblastin induces tumor suppressive phenotype and enhances chemosensitivity to doxorubicin via Src-Stat3 inactivation in osteosarcoma.
|
ジャーナル |
Sci Rep
|
Abstract |
Ameloblastin (AMBN), the most abundant non-amelogenin enamel matrix protein, plays a role in ameloblast differentiation. Previously, we found that AMBN promoted osteogenic differentiation via the interaction between CD63 and integrin β1, leading to the inactivation of Src; however, how AMBN affects the malignant behavior of osteosarcoma is still unclear. Osteosarcoma affects the bone and is associated with poor prognosis because of the high rate of pulmonary metastases and drug resistance. Here we demonstrated that stable overexpression of AMBN induced apoptosis and suppressed colony formation and cell migration via the inactivation of Src-Stat3 pathway in human osteosarcoma cells. Moreover, AMBN induced chemosensitivity to doxorubicin. Thus, AMBN induced a tumor suppressive phenotype and chemosensitivity to doxorubicin via the AMBN-Src-Stat3 axis in osteosarcoma. Indeed, immunohistochemical expression of AMBN was significantly correlated with better outcome of osteosarcoma patients. Our findings suggest that AMBN can be a new prognostic marker and therapeutic target for osteosarcoma combined with conventional doxorubicin treatment.
|
巻・号 |
7
|
ページ |
40187
|
公開日 |
2017-1-5
|
DOI |
10.1038/srep40187
|
PII |
srep40187
|
PMID |
28054649
|
PMC |
PMC5214574
|
MeSH |
Animals
Antibiotics, Antineoplastic / pharmacology*
Apoptosis
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Cell Survival / drug effects
Dental Enamel Proteins / metabolism*
Disease Models, Animal
Doxorubicin / pharmacology*
Humans
Immunohistochemistry
Mice, Nude
Models, Biological
Neoplasm Transplantation
Oncogene Protein pp60(v-src) / antagonists & inhibitors*
Osteosarcoma / drug therapy*
Osteosarcoma / pathology
STAT3 Transcription Factor / antagonists & inhibitors*
Treatment Outcome
|
IF |
3.998
|
引用数 |
8
|
リソース情報 |
ヒト・動物細胞 |
NOS-1(RCB1032) |