Transcriptomics,Genomics

Dataset Information

37

The intestinal adenocarcinomas of the cis-Apc/Smad4 compound mutant mice


ABSTRACT: Inactivation of TGF-beta family signaling is implicated in colorectal tumor progression. Using the cis-Apc/Smad4 mutant mice, a model of invasive colorectal cancer whose TGF-beta family signaling is blocked, we demonstrate here that a novel type of immature myeloid cells (iMCs) is recruited from the bone marrow to the tumor invasion front. These CD34+ iMCs express MMP9/2 and CC-chemokine receptor 1 (CCR1), and migrate toward its ligand CCL9. In the adenocarcinomas, expression of CCL9 is increased in the tumor epithelium. Such changes in the chemokine expression or the CD34+ iMC recruitment are not observed in the Apc (+/–) mice, a model of adenomatous polyposis. By knocking out Ccr1 gene in the cis-Apc/Smad4 mutant mice, we further demonstrate that lack of CCR1 prevents the accumulation of CD34+ iMCs at the invasion front and suppresses tumor invasion. These results indicate that loss of the TGF-beta family signaling in tumor epithelium causes accumulation of iMCs that help tumor invasion. Keywords: disease state analysis Overall design: We compared the gene expression profile of the cis-Apc/Smad4 adenocarcinomas with that of the Apc (+/–) adenomas to look for chemokines that were increased in the adenocarcinomas. To this end, we used DNA Chip Consortium Mouse Microarray v2.0 (oligonucleotide microarray) that contains 65-mer oligonuleotide probes for 21,997 mouse transcripts for three individual analyses.

INSTRUMENT(S): DNA Chip Consortium Mouse Microarray v2.0

SUBMITTER: Makoto Mark Taketo  

PROVIDER: GSE6950 | GEO | 2007-04-25

SECONDARY ACCESSION(S): PRJNA99341

REPOSITORIES: GEO

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Publications


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  ...[more]

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