論文 - 詳細
| RRC ID | 57557 |
|---|---|
| 著者 | Suzuki E, Yamazaki S, Naito T, Hashimoto H, Okubo S, Udagawa H, Goto K, Tsuboi M, Ochiai A, Ishii G. |
| タイトル | Secretion of high amounts of hepatocyte growth factor is a characteristic feature of cancer-associated fibroblasts with EGFR-TKI resistance-promoting phenotype: A study of 18 cases of cancer-associated fibroblasts. |
| ジャーナル | Pathol Int |
| Abstract |
Humoral factors from cancer-associated fibroblasts (CAFs) reportedly affect epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance in cancer cells with EGFR mutations. The aim of this study was to identify the robust humoral factors secreted from CAFs that induce the primary resistance to EGFR-TKI. We evaluated the EGFR-TKI sensitivity of EGFR-mutant lung adenocarcinoma cell line (PC-9) treated with condition media (CM) from 18 cases of CAFs and matched non-cancerous-tissue-associated fibroblasts (NCAFs). We measured the expression levels of hepatocyte growth factor (HGF), interleukin-6, fibroblast growth factor-2, insulin-like growth factor-1, and vascular endothelial growth factor-A in CAFs and NCAFs. We examined whether HGF neutralizing antibody could annul the EGFR-TKI resistance induced by CM from CAFs. Compared to CM from NCAFs, CM from CAFs increased the resistance of PC-9 cells to EGFR-TKI in five out of 18 cases. Relative expression ratio of HGF messenger RNA was significantly higher in these five CAFs compared to others (P = 0.0013), whereas other cytokines were not. In four of these five cases, the addition of HGF neutralizing antibody significantly decreased the survival ratio of PC-9 cells. This study suggests that the secretion of higher amounts of HGF is the robust feature of EGFR-TKI resistance-promoting CAFs. |
| 巻・号 | 69(8) |
| ページ | 472-480 |
| 公開日 | 2019-8-1 |
| DOI | 10.1111/pin.12838 |
| PMID | 31339210 |
| MeSH | Adenocarcinoma / metabolism Adult Aged Aged, 80 and over Cancer-Associated Fibroblasts / metabolism* Cell Line, Tumor Cell Survival / drug effects Drug Resistance, Neoplasm / physiology* ErbB Receptors / metabolism Female Hepatocyte Growth Factor / metabolism* Humans Lung Neoplasms / metabolism Male Middle Aged Phenotype* Protein Kinase Inhibitors / metabolism* Protein Kinase Inhibitors / pharmacology |
| IF | 2.082 |
| 引用数 | 2 |
| 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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| 各媒体での言及数の合計 | 0 |
| 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 | |
| 遺伝子材料 | CS-CDF-CG-PRE (RDB04379) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |