Tumorigenic Cells Are Common in Mouse MPNSTs but Their Frequency Depends upon Tumor Genotype and Assay Conditions

SummaryTumor-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.

► Many MPNST cells have the potential to form tumors
► Some sarcomas contain high frequencies of tumor-initiating cells
► Tumors of different genotypes require different assays to detect tumorigenic cells
► Laminin promotes clonogenic growth but can be intrinsic or extrinsic to MPNST cells