In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 3377-3377
Abstract:
In cancer treatment, stroma-derived microenvironmental cues are suspected to exert an adversary impact on anti-cancer drug efficacy. In order to take such influences into account in cellular drug screening campaigns, we have set up a high-throughput-compatible co-spheroid model, enabling the analysis of various combinations of cancer and stroma cell lines. This assay system allows for cell analysis in a three-dimensional (3D) close-to-physiological environment with simultaneous detection of cancer and stroma cell viability based on differential luciferase cell-labelling. Our data revealed that growth characteristics strongly depend on the specific cell types combined. Stroma cells in contrast to tumor cells usually ceased to proliferate or even showed dramatic loss of viability possibly due to metabolic hijacking. We report on the optimization of the cellular test systems to ensure significant viable stroma cell counts during the drug testing phase. In such an optimized co-spheroid model of Firefly-luciferase labelled DLD-1 colon cancer cells with Renilla-luciferase labelled HS27A stroma cells, we identified the MEK kinase inhibitor Trametinib as a compound showing a 10-30fold attenuated potency as compared to the DLD-1 mono-spheroid model. Based on these results we suggest integrating optimized co-spheroid studies into early drug development to focus on compounds that remain active under microenvironmental conditions. Citation Format: Claudia Hoffmann, Daniel Feger, Oliver Siedentopf, Holger Weber, Sarah Umber, Jan E. Ehlert. Co-spheroid analysis reveals attenuating effect of HS27A stroma cells on DLD1 colon carcinoma susceptibility to MEK kinase inhibitor trametinib. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3377. doi:10.1158/1538-7445.AM2015-3377
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2015-3377
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2015
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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