Colorectal cancer-derived tumor spheroids retain the characteristics of original tumors

Cancer Lett. 2015 Oct 10;367(1):34-42. doi: 10.1016/j.canlet.2015.06.024. Epub 2015 Jul 13.

Abstract

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.

Keywords: Colorectal cancer; Spheroid cultures; Xenograft.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antineoplastic Agents / pharmacology
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Cetuximab
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • DNA Fingerprinting
  • DNA Mutational Analysis
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm
  • Female
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Mutation
  • Neoplasm Transplantation
  • Neoplastic Stem Cells* / drug effects
  • Neoplastic Stem Cells* / metabolism
  • Neoplastic Stem Cells* / pathology
  • Protein Kinase Inhibitors / pharmacology
  • Republic of Korea
  • Spheroids, Cellular
  • Time Factors
  • Tumor Burden
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • Cetuximab