RRC ID |
38360
|
著者 |
Yamazoe H, Hagihara Y, Kobayashi H.
|
タイトル |
Multicomponent Coculture System of Cancer Cells and Two Types of Stromal Cells for In Vitro Evaluation of Anticancer Drugs.
|
ジャーナル |
Tissue Eng Part C Methods
|
Abstract |
In vitro evaluation of anticancer drugs using cancer cells has long been performed for the development of novel drugs and the selection of effective drugs for different patients. Recent studies have suggested that tumor stromal cells affect the drug sensitivity of cancer cells; however, most conventional culture systems for drug evaluation lack stromal cells. In this study, we fabricated a multicomponent coculture system that takes account of cancer-stroma interactions for drug evaluation. In this system, small-cell and nonsmall-cell lung cancer cells embedded in collagen gel were cocultured with two types of stromal cells, including stromal fibroblasts and proinflammatory cytokine-secreting monocytes, thus recreating the in vivo cancer microenvironment. Cancer drug sensitivity was significantly altered by the presence of stromal cells. Fibroblasts induced resistance of cancer cells to anticancer drugs. Monocytes induced the upregulation of thymidine phosphorylase in cancer cells, promoting the conversion of an anticancer prodrug to a cytotoxic drug, and consequently enhanced the sensitivity of cancer cells to the anticancer prodrug. These results clearly show the importance of incorporating stromal cells into culture systems for drug evaluation. Our system will help to improve the accuracy of in vitro drug evaluation and provide useful information for the in vitro recreation of cancer microenvironments.
|
巻・号 |
22(1)
|
ページ |
20-9
|
公開日 |
2016-1-1
|
DOI |
10.1089/ten.TEC.2015.0188
|
PMID |
26421875
|
MeSH |
Animals
Antineoplastic Agents / administration & dosage*
Cell Communication / drug effects*
Cell Line, Tumor
Cells, Cultured
Coculture Techniques / instrumentation*
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical / instrumentation*
Equipment Design
Equipment Failure Analysis
Humans
Mice
Neoplasms, Experimental / drug therapy*
Neoplasms, Experimental / pathology
Stromal Cells / drug effects*
Stromal Cells / pathology
Treatment Outcome
Tumor Microenvironment / drug effects
|
IF |
3.508
|
引用数 |
4
|
WOS 分野
|
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
CELL & TISSUE ENGINEERING
CELL BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
WA-mFib(RCB1925)
A549(RCB0098) |