論文 - 詳細
| RRC ID | 54858 |
|---|---|
| 著者 | Masuda T, Nakashima T, Namba M, Yamaguchi K, Sakamoto S, Horimasu Y, Miyamoto S, Iwamoto H, Fujitaka K, Miyata Y, Hamada H, Okada M, Hattori N. |
| タイトル | Inhibition of PAI-1 limits chemotherapy resistance in lung cancer through suppressing myofibroblast characteristics of cancer-associated fibroblasts. |
| ジャーナル | J Cell Mol Med |
| Abstract |
Plasminogen activator inhibitor-1 (PAI-1) promotes pulmonary fibrosis through increasing myofibroblast (MF) characteristics, expressing alpha-smooth muscle actin (α-SMA) in fibroblasts. Fibroblasts in the tumour stroma are called cancer-associated fibroblasts (CAFs). Some CAFs have MF characteristics and substantially promote tumour progression and chemotherapy resistance. This study determined whether inhibition of PAI-1 suppressed MF characteristics of CAFs and limited chemotherapy resistance in lung cancer. To investigate cellular PAI-1 expression and its correlation with α-SMA expression of CAFs, 34 patients' paraffin-embedded lung adenocarcinoma tissue sections were immunohistochemically stained for PAI-1 and α-SMA. Immunohistochemical analysis of lung adenocarcinoma tissues showed that PAI-1 expression was correlated with that of α-SMA (r = 0.71, p < 0.001). Furthermore, in vitro, α-SMA expression of CAFs was limited by PAI-1 inhibition, and apoptosis of CAFs was increased. In addition, the effectiveness of cisplatin on lung cancer cells co-cultured with CAFs was increased by suppressing α-SMA expression using PAI-1 inhibitor. In lung adenocarcinoma tissues, PAI-1 expression was associated with T factor and TNM stage. Our data suggest that inhibition of PAI-1 increased the chemotherapeutic effect on lung cancer through suppressing the MF characteristics of CAFs. Hence, PAI-1 might be a promising therapeutic target for patients with chemotherapeutic-resistant lung cancer with CAFs. |
| 巻・号 | 23(4) |
| ページ | 2984-2994 |
| 公開日 | 2019-4-1 |
| DOI | 10.1111/jcmm.14205 |
| PMID | 30734495 |
| PMC | PMC6433668 |
| MeSH | Aged Aged, 80 and over Animals Antineoplastic Agents / pharmacology* Apoptosis Biomarkers, Tumor / analysis* Cancer-Associated Fibroblasts / drug effects* Cancer-Associated Fibroblasts / metabolism Cancer-Associated Fibroblasts / pathology Cell Cycle Cell Proliferation Drug Resistance, Neoplasm* Female Follow-Up Studies Gene Expression Regulation, Neoplastic Humans Lung Neoplasms / drug therapy* Lung Neoplasms / metabolism Lung Neoplasms / pathology Male Mice Mice, Inbred C57BL Middle Aged Myofibroblasts / drug effects* Myofibroblasts / metabolism Myofibroblasts / pathology Plasminogen Activator Inhibitor 1 / chemistry* Plasminogen Activator Inhibitor 1 / metabolism Prognosis Retrospective Studies Tumor Cells, Cultured |
| IF | 4.658 |
| 引用数 | 1 |
| 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-9(RCB4455) A549 |