References
Query Results -- Details
MGI Accession ID: MGI:3820765
J Number: J:142240
Other Accession IDs:
Title: 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.
Authors: Kim YC; Clark RJ; Ranheim EA; Alexander CM
Journal: Cancer Res
Volume: 68
Issue: 24
Date: 2008 Dec 15
Year: 2008
Pages: 10145-53
Review Status: Peer Reviewed
Abstract:
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.
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