Changes of heterogeneous cell populations in the Ishikawa cell line during long-term culture: Proposal for an in vitro clonal evolution model of tumor cells.
Genomic changes in tumor cell lines can occur during culture, leading to differences between cell lines carrying the same name. In this study, genome profiles between low and high passages were investigated in the Ishikawa 3-H-12 cell line (JCRB1505). Cells contained between 43 and 46 chromosomes and the modal number changed from 46 to 45 during culture. Cytogenetic analysis revealed that a translocation t(9;14), observed in all metaphases, is a robust marker for this cell line. Single-nucleotide polymorphism microarrays showed a heterogeneous copy number in the early passages and distinct profiles at late passages. These results demonstrate that cell culture can lead to elimination of ancestral clones by sequential selection, resulting in extensive replacement with a novel clone. Our observations on Ishikawa cells in vitro are different from the in vivo heterogeneity in which ancestral clones are often retained during tumor evolution and suggest a model for in vitro clonal evolution.
Japanese Collection of Research Bioresources (JCRB) Cell Bank, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan. Electronic address: k-230@umin.ac.jp.
Fumio
F
Kasai
Japanese Collection of Research Bioresources (JCRB) Cell Bank, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
Noriko
N
Hirayama
Japanese Collection of Research Bioresources (JCRB) Cell Bank, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
Midori
M
Ozawa
Japanese Collection of Research Bioresources (JCRB) Cell Bank, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
Masashi
M
Iemura
Japanese Collection of Research Bioresources (JCRB) Cell Bank, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
Arihiro
A
Kohara
D018929:Cell Culture Techniques / Q000379:methods*; D002460:Cell Line; D002875:Chromosomes / Q000235:genetics; D060965:Clonal Evolution / Q000235:genetics*; D020732:Cytogenetic Analysis; D018740:Genetic Heterogeneity; D006801:Humans; D007621:Karyotyping; D046228:Microarray Analysis; D020641:Polymorphism, Single Nucleotide; D014178:Translocation, Genetic / Q000235:genetics
Cell culture passage; Cell line authentication; Chromosome rearrangements; Genome instability; Tumor heterogeneity