| RRC ID |
11911
|
| 著者 |
Hoshino A, Ishii G, Ito T, Aoyagi K, Ohtaki Y, Nagai K, Sasaki H, Ochiai A.
|
| タイトル |
Podoplanin-positive fibroblasts enhance lung adenocarcinoma tumor formation: podoplanin in fibroblast functions for tumor progression.
|
| ジャーナル |
Cancer Res
|
| Abstract |
During the metastatic process, cancer cells interact with vascular adventitial fibroblasts (VAF), which are the main components of the outermost connective tissue layer of blood vessels. This activity suggests the presence of a specific tumor microenvironment in the perivascular area. The s.c. coinjection of human lung adenocarcinoma cell lines (A549, PC-14, and CRL-5807) and human VAF (hVAF) resulted in a high rate of tumor formation, compared with the coinjection of these cell lines and human lung tissue-derived fibroblasts (hLF). A cDNA microarray analysis revealed a higher expression level of podoplanin in hVAFs than in hLFs (4.7-fold). Flow cytometry analysis also showed a higher expression level of podoplanin in hVAFs (43% ± 17.5%) than in hLFs (16% ± 10.3%). Sorted podoplanin-positive hVAFs displayed enhanced tumor formation, lymph node metastasis, and lung metastasis of A549 compared to sorted podoplanin-negative hVAFs. Knockdown of podoplanin in hVAFs decreased the augmenting effect of tumor formation and in vitro colony formation. The overexpression of podoplanin in hVAFs hastened the tumor formation of A549, compared with control hVAFs. Furthermore, the analysis of small-sized human lung adenocarcinoma (n = 112) revealed that patients with podoplanin-positive cancer-associated fibroblasts had a significantly higher rate of lymph node metastasis and a high risk of recurrence. These results indicate a promotive effect of hVAFs mediated by podoplanin on cancer progression and suggest that the perivascular environment may constitute a specific niche for tumor progression.
|
| 巻・号 |
71(14)
|
| ページ |
4769-79
|
| 公開日 |
2011-7-15
|
| DOI |
10.1158/0008-5472.CAN-10-3228
|
| PII |
0008-5472.CAN-10-3228
|
| PMID |
21610106
|
| MeSH |
Adenocarcinoma / blood supply
Adenocarcinoma / genetics
Adenocarcinoma / metabolism*
Adenocarcinoma / pathology*
Adenocarcinoma of Lung
Animals
Cell Communication / physiology*
Cell Line, Tumor
Connective Tissue / metabolism*
Connective Tissue / pathology
Disease Progression
Fibroblasts / metabolism*
Fibroblasts / pathology*
Flow Cytometry
Humans
Lung Neoplasms / blood supply
Lung Neoplasms / genetics
Lung Neoplasms / metabolism*
Lung Neoplasms / pathology*
Membrane Glycoproteins / biosynthesis*
Mice
Mice, SCID
Neoplastic Stem Cells / metabolism
Neoplastic Stem Cells / pathology
Transplantation, Heterologous
|
| IF |
9.727
|
| 引用数 |
106
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
PC-14(RCB0446)
A549(RCB0098) |
