title: Tumorigenic cells are common in mouse MPNSTs but their frequency depends upon tumor genotype and assay conditions.
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.
authors.affiliation: Department of Internal Medicine, Life Sciences Institute, and Center for Stem Cell Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA.
authors.forename: Johanna
authors.initials: J
authors.lastname: Buchstaller
authors.forename: Paul E
authors.initials: PE
authors.lastname: McKeever
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Morrison
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D005838:Genotype; D019012:Integrin beta1 / Q000378:metabolism / Q000502:physiology; D007797:Laminin / Q000378:metabolism; D051379:Mice; D018317:Nerve Sheath Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D019012:Integrin beta1; D007797:Laminin