Tmod-18. Three-dimensional Microtumors in Physiologic Microenvironments Maintain Brain Tumor Initiating Cells
Year: 2016
Type: conference-abstract
Abstract: Elucidation of mechanisms of brain tumor initiating cell (BTIC) maintenance and therapeutic resistance offers great promise for development of novel anti-tumor treatments. Current leading studies rely on BTIC isolation from patient-derived xenografts followed by propagation as neurospheres. As this process is expensive and time-consuming, we determined if three-dimensional microtumors were an alternative in vitro method for modeling tumor growth via BITC maintenance and/or enrichment. Brain tumor cells were grown as neurospheres or as microtumors produced using a human-derived biomatrix HuBiogelTM and maintained with physiologically relevant microenvironments. Percentages of BITCs were then determined based on cell surface marker expression (CD133), label retention (carboxyfluorescein succinimidyl ester; CFSE), and tumorsphere formation capacity. Our data demonstrate that expansion of brain tumor cells as hypoxic and nutrient restricted microtumors significantly increased the percentage of both CD133+ and CFSE+ cells. For example, fifteen percent of all brain tumor cells from a xenograft propagated as microtumors were CD133+, whereas only one percent of neurosphere cultured cells expressed the BTIC marker. Relative to CD133, CFSE was retained in a higher percentage of cells, but CFSE+ cells were still increased in the microtumor condition in comparison to neurospheres. We further demonstrate that BTIC-marker positive cells isolated from microtumors maintain neurosphere formation capacity in the in vitro limiting dilution assay and tumorigenic potential in vivo. These data demonstrate that microtumors can be a useful three-dimensional biological model for the study of BTIC maintenance and targeting.
Source: Neuro-Oncology
Authors: Ashley Gilbert, Kiera Walker, Anh Tran, Yancey Gillespie, Raj Singh, Anita Hjelmeland
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2586841245