| RRC ID |
57557
|
| Author |
Suzuki E, Yamazaki S, Naito T, Hashimoto H, Okubo S, Udagawa H, Goto K, Tsuboi M, Ochiai A, Ishii G.
|
| Title |
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.
|
| Journal |
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.
|
| Volume |
69(8)
|
| Pages |
472-480
|
| Published |
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
|
| Times Cited |
2
|
| Resource |
| DNA material |
CS-CDF-CG-PRE (RDB04379)
pCAG-HIVgp (RDB04394)
pCMV-VSV-G-RSV-Rev (RDB04393) |
