Chemically-induced cancers do not originate from bone marrow-derived cells

PLoS One. 2012;7(1):e30493. doi: 10.1371/journal.pone.0030493. Epub 2012 Jan 24.


Background: The identification and characterization of cancer stem cells (CSCs) is imperative to understanding the mechanism of cancer pathogenesis. Growing evidence suggests that CSCs play critical roles in the development and progression of cancer. However, controversy exists as to whether CSCs arise from bone marrow-derived cells (BMDCs).

Methodology and principal findings: In the present study, n-nitrosodiethylamine (DEN) was used to induce tumor formation in female mice that received bone marrow from male mice. Tumor formation was induced in 20/26 mice, including 12 liver tumors, 6 lung tumors, 1 bladder tumor and 1 nasopharyngeal tumor. Through comparison of fluorescence in situ hybridization (FISH) results in corresponding areas from serial tumor sections stained with H&E, we determined that BMDCs were recruited to both tumor tissue and normal surrounding tissue at a very low frequency (0.2-1% in tumors and 0-0.3% in normal tissues). However, approximately 3-70% of cells in the tissues surrounding the tumor were BMDCs, and the percentage of BMDCs was highly associated with the inflammatory status of the tissue. In the present study, no evidence was found to support the existence of fusion cells formed form BMDCs and tissue-specific stem cells.

Conclusions: In summary, our data suggest that although BMDCs may contribute to tumor progression, they are unlike to contribute to tumor initiation.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormal Karyotype / chemically induced
  • Animals
  • Bone Marrow Cells / pathology*
  • Bone Marrow Transplantation / adverse effects
  • Bone Marrow Transplantation / physiology
  • Carcinogens*
  • Cell Transformation, Neoplastic / pathology*
  • Diethylnitrosamine
  • Female
  • In Situ Hybridization, Fluorescence
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / chemically induced*
  • Neoplasms / epidemiology
  • Neoplasms / pathology
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology*
  • Sex Chromosome Aberrations / chemically induced
  • Sex Chromosomes / metabolism


  • Carcinogens
  • Diethylnitrosamine