Abstract:
:Inactivation of TGF-beta family signaling is implicated in colorectal tumor progression. Using cis-Apc(+/Delta716) Smad4(+/-) mutant mice (referred to as cis-Apc/Smad4), a model of invasive colorectal cancer in which TGF-beta family signaling is blocked, we show here that a new type of immature myeloid cell (iMC) is recruited from the bone marrow to the tumor invasion front. These CD34(+) iMCs express the matrix metalloproteinases MMP9 and MMP2 and the CC-chemokine receptor 1 (CCR1) and migrate toward the CCR1 ligand CCL9. In adenocarcinomas, expression of CCL9 is increased in the tumor epithelium. By deleting Ccr1 in the background of the cis-Apc/Smad4 mutant, we further show that lack of CCR1 prevents accumulation of CD34(+) iMCs at the invasion front and suppresses tumor invasion. These results indicate that loss of transforming growth factor-beta family signaling in tumor epithelium causes accumulation of iMCs that promote tumor invasion.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Kitamura T,Kometani K,Hashida H,Matsunaga A,Miyoshi H,Hosogi H,Aoki M,Oshima M,Hattori M,Takabayashi A,Minato N,Taketo MMdoi
10.1038/ng1997subject
Has Abstractpub_date
2007-04-01 00:00:00pages
467-75issue
4eissn
1061-4036issn
1546-1718pii
ng1997journal_volume
39pub_type
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