| 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
|
| リソース情報 |
| ヒト・動物細胞 |
PC-9(RCB4455) |
