Author(s): PylayevaGupta Y, Lee KE, Hajdu CH, Miller G, BarSagi D
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Abstract Stromal responses elicited by early stage neoplastic lesions can promote tumor growth. However, the molecular mechanisms that underlie the early recruitment of stromal cells to sites of neoplasia remain poorly understood. Here, we demonstrate an oncogenic Kras(G12D)-dependent upregulation of GM-CSF in mouse pancreatic ductal epithelial cells (PDECs). An enhanced GM-CSF production is also observed in human PanIN lesions. Kras(G12D)-dependent production of GM-CSF in vivo is required for the recruitment of Gr1(+)CD11b(+) myeloid cells. The suppression of GM-CSF production inhibits the in vivo growth of Kras(G12D)-PDECs, and, consistent with the role of GM-CSF in Gr1(+)CD11b(+) mobilization, this effect is mediated by CD8(+) T cells. These results identify a pathway that links oncogenic activation to the evasion of antitumor immunity. Copyright © 2012 Elsevier Inc. All rights reserved.
This article was published in Cancer Cell
and referenced in Journal of Genetic Syndromes & Gene Therapy