Gene expression of primary MMTV-Neu tumors compared to secondary tumors generated from lin- and single tumor initiating cell (TIC) transplantation. Mus musculus

Most solid tumors seem to be organized in a hierarchy in which only a fraction of cells, termed tumor-initiating cells (TICs), is capable of disseminating new tumors after transplantation into recipient mice. However, whether a single TIC can induce a tumor or whether it requires additional TICs or non-TICs for tumor initiation is not known. Here we show that injections of single CD24+:Jag1- cells from Her2/Neu+ mammary tumors into recipient mammary glands induced tumors at a frequency of 1/22. Single cell-derived secondary tumors exhibited histology, flow cytometry and global expression profiles that were indistinguishable from primary tumors. Thus, a single TIC can act cell autonomously to induce a tumor and therefore complete eradication of all TICs would be required to cure cancer. Overall design: Total RNA obtained from primary MMTV-Neu tumors, secondary tumors generated by lin- cell transplantation, and secondary tumors generated by a single TIC, were used for microarray analysis to determine differentially regulated genes in the secondary tumors. Cluster analysis based on gene expression were then performed to assess tumor similarity