| RRC ID |
51722
|
| 著者 |
Kayamori K, Katsube K, Sakamoto K, Ohyama Y, Hirai H, Yukimori A, Ohata Y, Akashi T, Saitoh M, Harada K, Harada H, Yamaguchi A.
|
| タイトル |
NOTCH3 Is Induced in Cancer-Associated Fibroblasts and Promotes Angiogenesis in Oral Squamous Cell Carcinoma.
|
| ジャーナル |
PLoS One
|
| Abstract |
Recent studies have shown that Notch signaling is involved in many types of cancers, including oral squamous cell carcinomas (OSCCs). However, the role of Notch signaling in the tumor microenvironment is not yet fully understood. In this study, we investigated the roles of NOTCH3 signaling in cancer associated fibroblasts (CAFs) in OSCCs. Immunohistochemical study of 93 human tongue OSCC cases indicated that about one third of OSCCs showed NOTCH3 expression in CAFs, and that this expression significantly correlated with tumor-size. In vitro study showed that OSCC cell lines, especially HO1-N-1 cells stimulated NOTCH3 expression in normal human dermal fibroblasts (NHDFs) through direct cell-to-cell contact. Immunohistochemical and morphometric analysis using human OSCC samples demonstrated that NOTCH3 expression in CAFs significantly correlated with micro-vessel density in cancer stroma. In vitro angiogenesis assays involving co-culture of NHDFs with HO1-N-1 and human umbilical endothelial cells (HUVECs), and NOTCH3 knockdown in NHDFs using siRNA, demonstrated that HO1-N-1 cells significantly promoted tube formation dependent on NOTCH3-expression in NHDFs. Moreover, NOTCH3 expression in CAFs was related to poor prognosis of the OSCC patients. This work provides a new insight into the role of Notch signaling in CAFs associated with tumor angiogenesis and the possibility of NOTCH3-targeted molecular therapy in OSCCs.
|
| 巻・号 |
11(4)
|
| ページ |
e0154112
|
| 公開日 |
2016-1-1
|
| DOI |
10.1371/journal.pone.0154112
|
| PII |
PONE-D-15-55869
|
| PMID |
27124156
|
| PMC |
PMC4849776
|
| MeSH |
Adult
Aged
Carcinoma, Squamous Cell / diagnosis
Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / mortality
Carcinoma, Squamous Cell / pathology
Cell Communication
Coculture Techniques
Female
Fibroblasts / metabolism*
Fibroblasts / pathology
Gene Expression Regulation, Neoplastic*
Human Umbilical Vein Endothelial Cells / metabolism
Human Umbilical Vein Endothelial Cells / pathology
Humans
Male
Middle Aged
Mouth Neoplasms / diagnosis
Mouth Neoplasms / genetics*
Mouth Neoplasms / mortality
Mouth Neoplasms / pathology
Neovascularization, Pathologic / genetics*
Neovascularization, Pathologic / metabolism
Neovascularization, Pathologic / pathology
Prognosis
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Receptor, Notch3 / antagonists & inhibitors
Receptor, Notch3 / genetics*
Receptor, Notch3 / metabolism
Signal Transduction
Survival Analysis
Tumor Burden
Tumor Cells, Cultured
Tumor Microenvironment
|
| IF |
2.74
|
| 引用数 |
17
|
| リソース情報 |
| ヒト・動物細胞 |
MKN74(RCB1002)
HeLa
A549 |
