期刊
CANCER LETTERS
卷 367, 期 1, 页码 34-42出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2015.06.024
关键词
Spheroid cultures; Colorectal cancer; Xenograft
类别
资金
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI11C1300]
- National Research Foundation of Korea (NRF) - Korea government (MSIP) [NRF-2012R1A2A1A03670452]
- Ministry of Health, Welfare and affairs
Primary cultures of cancer cells are useful for developing personalized medicine. In this study, we characterized three lines of three-dimensional (3D) tumor spheroids established directly from tumor tissues of patients with colorectal cancers (CRCs). Each line mainly included EpCAM-positive cells and cells expressing putative cancer stem cell markers such as CD133, CD44, CD24, ALDH1, and LGR5. These characteristic stem cell markers remained identically for months in vitro. Short tandem repeat genotyping suggested that genetic fingerprints of these tumor spheroids were similar to those of the original tumor tissues from which they were derived. Mutational analysis showed that each line had the same mutation profile for APC, KRAS, MLH1, serine threonine kinase 11, and TP53 as its parental tumor tissue. One line harboring an activating KRAS mutation was resistant to cetuximab while the remaining two lines harboring wild-type KRAS showed different responses to cetuximab. Immunohistochemical analysis showed that xenograft tumors derived from these lines retained the histopathological and mutational patterns of their parental tumors. Collectively, these results clearly showed that 3D tumor spheroids directly generated from tumor tissues of patients with CRCs preserved the characteristics of their parental tumor tissues and could be used for developing personalized medicines for CRCs. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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