論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | PC-14(RCB0446) A549(RCB0098) |