論文 - 詳細
| RRC ID | 57423 |
|---|---|
| 著者 | Nakamura H, Sugano M, Miyashita T, Hashimoto H, Ochiai A, Suzuki K, Tsuboi M, Ishii G. |
| タイトル | Organoid culture containing cancer cells and stromal cells reveals that podoplanin-positive cancer-associated fibroblasts enhance proliferation of lung cancer cells. |
| ジャーナル | Lung Cancer |
| Abstract |
OBJECTIVE:Podoplanin-positive cancer-associated fibroblasts (CAFs) play an important role in tumor progression. The aim of this study was to evaluate the effect of podoplanin (+) CAFs on the proliferation of cancer cells using a three-dimensional (3D) organoid model. MATERIALS AND METHODS:We examined the success rate of organoid culture containing PC-9 cancer cells and CAFs. Thereafter, we compared the proliferating index (MIB-1 index) of PC-9 cells co-cultured with podoplanin-overexpressing CAFs and control CAFs using organoid specimens. Furthermore, we compared the MIB-1 labeling index of cancer cells in podoplanin (+) CAFs cases (n = 13) and podoplanin (-) CAFs cases (n = 14) using surgically resected adenocarcinoma specimens. RESULTS:Without CAFs, PC-9 cells did not form any organoid (success rate: 0%). When PC-9 cells were mixed with CAFs (1:10), the mixed cells generated round and steric aggregates (hybrid cancer organoids, success rate: 100%). In three independent experiments, the MIB-1 index of PC-9 cells in hybrid cancer organoids containing podoplanin-overexpressing CAFs was significantly higher than that of PC-9 cells in organoids containing control CAFs (Exp. 1: 40.4% vs. 24.4%; Exp. 2: 40.0% vs. 24.5%; Exp. 3: 40.3% vs. 25.2%; p < 0.001). Surgically resected human tumors revealed that the MIB-1 index of adenocarcinoma cells was significantly higher in the case of podoplanin (+) CAFs than in the case of podoplanin (-) CAFs (34.8% vs. 16.2%; p < 0.01). CONCLUSION:Our data suggested that the hybrid cancer organoid model might reflect the growth-promoting effect of podoplanin (+) CAFs in cancer cells, and this new system can be a useful tool for evaluating the tumor microenvironment. |
| 巻・号 | 134 |
| ページ | 100-107 |
| 公開日 | 2019-8-1 |
| DOI | 10.1016/j.lungcan.2019.04.007 |
| PII | S0169-5002(19)30394-0 |
| PMID | 31319967 |
| MeSH | Biomarkers, Tumor Cancer-Associated Fibroblasts / metabolism* Cancer-Associated Fibroblasts / pathology* Cell Line, Tumor Cell Proliferation Gene Expression Humans Immunohistochemistry Lung Neoplasms / metabolism* Lung Neoplasms / pathology* Membrane Glycoproteins / genetics Membrane Glycoproteins / metabolism* Organoids Stromal Cells / metabolism* Stromal Cells / pathology* Tissue Culture Techniques Tumor Microenvironment |
| IF | 4.599 |
| 引用数 | 4 |
| リソース情報 | |
| 遺伝子材料 | pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |