| First Author | Kim YC | Year | 2008 |
| Journal | Cancer Res | Volume | 68 |
| Issue | 24 | Pages | 10145-53 |
| PubMed ID | 19074881 | Mgi Jnum | J:142240 |
| Mgi Id | MGI:3820765 | Doi | 10.1158/0008-5472.CAN-08-2992 |
| Citation | Kim YC, et al. (2008) Wnt1 expression induces short-range and long-range cell recruitments that modify mammary tumor development and are not induced by a cell-autonomous beta-catenin effector. Cancer Res 68(24):10145-53 |
| abstractText | Xenograft model studies have shown that tumor-associated, or genetically modified, activated stromal cells can promote tumor cell growth. Here, we examined mammary tumors arising in response to two different transgene-mediated Wnt signaling effectors: Wnt1 (a ligand with cell-nonautonomous effects) and DeltaNbeta-catenin (a constitutively active form of the intracellular effector). Although the route of tumor development has been shown to be similar for these two models, histologic analysis shows that Wnt1-induced tumors are associated with tracts of activated stroma, whereas most DeltaNbeta-catenin-induced tumors are solid adenocarcinomas. Furthermore, quantification of the 'reactive stroma index' indicates that abundant activated stroma correlates with accelerated tumor progression. Wnt1-expressing mammary epithelial cells induce Wnt-specific target gene expression in local stromal cells (Wnt1-induced secreted protein 1/CCN4) but also induce long-range effects. Thus, mice with rapid tumor progression have 2-fold more circulating endothelial progenitor cells in peripheral blood than control or DeltaNbeta-catenin transgenic mice. Using tagged bone marrow (BM) transplants, we show that BM-derived cells are massively recruited to infiltrate the stroma of Wnt1-induced tumors where they differentiate into multiple cell types. Thus, localized ectopic expression of the proto-oncogene Wnt1 in mammary glands induces systemic responses, and we propose that this response modifies the tumorigenic outcome. |
