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Multicomponent Coculture System of Cancer Cells and Two Types of Stromal Cells for In Vitro Evaluation of Anticancer Drugs.
- Source :
-
Tissue engineering. Part C, Methods [Tissue Eng Part C Methods] 2016 Jan; Vol. 22 (1), pp. 20-9. Date of Electronic Publication: 2015 Nov 04. - Publication Year :
- 2016
-
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.
- Subjects :
- Animals
Cell Line, Tumor
Cells, Cultured
Dose-Response Relationship, Drug
Equipment Design
Equipment Failure Analysis
Humans
Mice
Neoplasms, Experimental pathology
Stromal Cells pathology
Treatment Outcome
Tumor Microenvironment drug effects
Antineoplastic Agents administration & dosage
Cell Communication drug effects
Coculture Techniques instrumentation
Drug Evaluation, Preclinical instrumentation
Neoplasms, Experimental drug therapy
Stromal Cells drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1937-3392
- Volume :
- 22
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Tissue engineering. Part C, Methods
- Publication Type :
- Academic Journal
- Accession number :
- 26421875
- Full Text :
- https://doi.org/10.1089/ten.TEC.2015.0188