Tumorigenic cells are common in mouse MPNSTs but their frequency depends upon tumor genotype and assay conditions

Cancer Cell. 2012 Feb 14;21(2):240-52. doi: 10.1016/j.ccr.2011.12.027.

Abstract

Tumor-initiating cells have been suggested to be rare in many cancers. We tested this in mouse malignant peripheral nerve sheath tumors (MPNSTs) and found that 18% of primary and 49% of passaged MPNST cells from Nf1(+/-); Ink4a/Arf(-/-) mice formed tumors upon transplantation, whereas only 1.8% to 2.6% of MPNST cells from Nf1(+/-); p53(+/-) mice did. MPNST cells of both genotypes require laminin binding to β1-integrin for clonogenic growth. Most MPNST cells from Nf1(+/-); Ink4a/Arf(-/-) mice expressed laminin, whereas most MPNST cells from Nf1(+/-); p53(+/-) mice did not. Exogenous laminin increased the percentage of MPNST cells from Nf1(+/-); p53(+/-) but not Nf1(+/-); Ink4a/Arf(-/-) mice that formed tumorigenic colonies. Tumor-forming potential is common among MPNST cells, but the assay conditions required to detect it vary with tumor genotype.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Cell Transformation, Neoplastic*
  • Genotype
  • Integrin beta1 / metabolism
  • Integrin beta1 / physiology
  • Laminin / metabolism
  • Mice
  • Nerve Sheath Neoplasms / genetics
  • Nerve Sheath Neoplasms / metabolism
  • Nerve Sheath Neoplasms / pathology*
  • Tumor Cells, Cultured

Substances

  • Integrin beta1
  • Laminin