| RRC ID |
43832
|
| 著者 |
Ito S, Ishii G, Hoshino A, Hashimoto H, Neri S, Kuwata T, Higashi M, Nagai K, Ochiai A.
|
| タイトル |
Tumor promoting effect of podoplanin-positive fibroblasts is mediated by enhanced RhoA activity.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
There is growing evidence that stromal fibroblasts can promote tumor progression via several mechanisms. We previously reported that podoplanin (PDPN) expressed on stromal fibroblasts is functionally protein responsible for the promotion of tumor formation in mouse subcutaneous tissue. The purpose of the present study was to reveal the molecular mechanism by which PDPN on stromal fibroblasts promotes tumor formation. The subcutaneous co-injection of the human lung adenocarcinoma cell line A549 and human fibroblasts (hFbs) overexpressing wild-type podoplanin (WT-PDPN) promoted subcutaneous tumor formation, compared with the co-injection of A549 and control hFbs (64% vs 21%). On the other hand, hFbs expressing PDPN mutant in which the cytoplasmic domain of PDPN was deleted (PDPN-Del.IC), resulted in a relatively lower level of tumor formation (33%). Since PDPN reportedly regulates RhoA activity through its cytoplasmic domain, we measured the activation state of RhoA in hFbs expressing WT-PDPN. RhoA activity was 2.7-fold higher in WT-PDPN expressing hFbs than in control hFbs. Furthermore, the subcutaneous co-injection of hFbs expressing constitutive active RhoA (G14VRhoA) and A549 cells enhanced tumor formation compared with the co-injection of the same cell line and control hFbs. These results indicate that enhanced RhoA activity in hFbs expressing PDPN may be one of the mechanisms resulting in the promotion of tumor formation, suggesting that biomechanical remodeling of the microenvironment by stromal fibroblasts may play important roles in tumor progression.
|
| 巻・号 |
422(1)
|
| ページ |
194-9
|
| 公開日 |
2012-5-25
|
| DOI |
10.1016/j.bbrc.2012.04.158
|
| PII |
S0006-291X(12)00847-9
|
| PMID |
22575513
|
| MeSH |
Animals
Cell Line, Tumor
Cytoplasm / metabolism
Dogs
Fibroblasts / metabolism
Fibroblasts / pathology*
Humans
Membrane Glycoproteins / genetics
Membrane Glycoproteins / metabolism*
Mice
Mutation
Neoplasms / enzymology
Neoplasms / pathology*
Protein Structure, Tertiary / genetics
rhoA GTP-Binding Protein / genetics
rhoA GTP-Binding Protein / metabolism*
|
| IF |
2.985
|
| 引用数 |
35
|
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
A549(RCB0098) |
