論文 - 詳細
| RRC ID | 62314 |
|---|---|
| 著者 | Lee JW, Sung JS, Park YS, Chung S, Kim YH. |
| タイトル | Identification of different gene expressions between diffuse- and intestinal-type spheroid-forming gastric cancer cells. |
| ジャーナル | Gastric Cancer |
| Abstract |
BACKGROUND:Three-dimensional in vitro spheroid models are unique because they are considered for enrichment of specific cell populations with self-renewal ability. In this study, we explored the different mechanisms of gastric cancer spheroid-forming cells according to the Lauren classification. METHODS:We isolated and enriched cells with self-renewal ability using spheroid-forming methods from gastric cancer cell lines. The expression of candidate target genes was investigated using western blot and qRT-PCR analysis. Lentiviral shRNA knockdown of target gene expression was performed and the effects on spheroid, colony forming, and tumorigenic ability were analyzed. RESULTS:The SNU-638, SNU-484, MKN-28, and NCI-N87 successfully formed spheroid from single cell and enriched for self-renewal ability from 11 gastric cancer cell lines, including diffuse and intestinal types. The expression of SOX2 and E-cadherin increased in spheroid-forming cells in a diffuse-type cell line (SNU-638 and SNU-484), but not in the intestinal type (MKN-28 and NCI-N87). In contrast, ERBB3 expression was only increased in intestinal-type spheroid cells. The depletion of each candidate target gene expression suppressed self-renewal ability to grow as spheroids and colonies in a soft agar assay. In particular, down-regulated ERBB3 in the intestinal-type cell lines inhibited tumor growth in a mouse xenograft model. We found that high ERBB3 gene expression correlates with decreased survival in the intestinal type of gastric cancer. CONCLUSIONS:Our results suggest that diffuse- and intestinal-type spheroid-forming cells express genes differently. Our data suggest that these candidate genes from spheroid-forming cells can be used in applications in targeted therapy. |
| 巻・号 | 22(5) |
| ページ | 967-979 |
| 公開日 | 2019-9-1 |
| DOI | 10.1007/s10120-019-00935-x |
| PII | 10.1007/s10120-019-00935-x |
| PMID | 30726523 |
| MeSH | Animals Apoptosis Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Cell Proliferation Gene Expression Profiling Gene Expression Regulation, Neoplastic* Humans Intestinal Neoplasms / genetics Intestinal Neoplasms / metabolism Intestinal Neoplasms / pathology* Male Mice Mice, Inbred BALB C Mice, Nude Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology* Spheroids, Cellular / metabolism Spheroids, Cellular / pathology* Stomach Neoplasms / genetics Stomach Neoplasms / metabolism Stomach Neoplasms / pathology* Tumor Cells, Cultured Xenograft Model Antitumor Assays |
| IF | 7.088 |
| リソース情報 | |
| ヒト・動物細胞 | MKN28(RCB1000) |