Primary cultures of human colon cancer as a model to study cancer stem cells

Tumour Biol. 2016 Sep;37(9):12833-12842. doi: 10.1007/s13277-016-5214-8. Epub 2016 Jul 23.

Abstract

The principal cause of death in cancer involves tumor progression and metastasis. Since only a small proportion of the primary tumor cells, cancer stem cells (CSCs), which are the most aggressive, have the capacity to metastasize and display properties of stem cells, it is imperative to characterize the gene expression of diagnostic markers and to evaluate the drug sensitivity in the CSCs themselves. Here, we have examined the key genes that are involved in the progression of colorectal cancer and are expressed in cancer stem cells. Primary cultures of colorectal cancer cells from a patient's tumors were studied using the flow cytometry and cytological methods. We have evaluated the clinical and stem cell marker expression in these cells, their resistance to 5-fluorouracil and irinotecan, and the ability of cells to form tumors in mice. The data shows the role of stem cell marker Oct4 in the resistance of primary colorectal cancer tumor cells to 5-fluorouracil.

Keywords: 5-Fu; CD133; Cancer stem cells; Colon cancer; Drug resistance; Oct4.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacology
  • Cell Line, Tumor
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Drug Resistance, Neoplasm / genetics*
  • Fluorouracil / pharmacology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Irinotecan
  • Mice
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays / methods

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Irinotecan
  • Fluorouracil
  • Camptothecin