Issues

Using a mouse model of breast cancer driven by Trp53 loss, Zhang and colleagues investigated the functional interaction between CD29^hiCD24^hi tumor-initiating cells (TIC) and a mesenchymal-like CD29^hiCD24^lo tumor cell subpopulation. These CD29^hiCD24^lo niche cells promoted the self-renewal capacity of TICs via secretion of soluble factors including WNT2 and chemokine (C-X-C motif) ligand 12 (CXCL12). Depletion of WNT2 and CXCL12 in CD29^hiCD24^lo niche cells or of the corresponding receptors in TICs impaired the ability of CD29^hiCD24^lo cells to promote TIC self-renewal in vitro. Furthermore, in limiting dilution transplantation assays, CD29^hiCD24^lo niche cells enhanced the tumor-initiating potential of TICs, which was decreased by knockdown of WNT2 in the CD29^hiCD24^lo subpopulation. These data highlight the importance of paracrine crosstalk between different tumor cell subpopulations in promoting tumor initiation. For details, please see the article by Zhang and colleagues on page 520.