Article Text
Abstract
Background and aims: SPARC (secreted protein acidic, rich in cysteine) is a matricellular protein that has been found to be activated in a number of human cancers. More recently, it has been shown to be upregulated in human gastric and colorectal cancer. We therefore wished to address the functional importance of SPARC upregulation to intestinal tumorigenesis in vivo.
Methods: SPARC upregulation was determined in intestinal adenomas of tumour-prone ApcMin/+ mice at both the RNA and the protein level. To determine the functional importance of SPARC for intestinal tumorigenesis we then intercrossed Sparc knockout mice with ApcMin/+ mice (n = 20). Intestinal enterocyte migration was examined using bromodeoxyuridine labelling studies.
Results: Levels of murine Sparc and several related proteins were upregulated in adenomas arising in ApcMin/+ mice. A deficiency of Sparc strongly suppressed adenoma formation in ApcMin/+ mice (p⩾0.0001). Importantly, a deficiency of Sparc also accelerated enterocyte migration (p = 0.01), as perturbed slow epithelial migration may underpin adenoma formation in the intestine.
Conclusions: These data implicate Sparc in both cell migration and tumour formation, and identify Sparc as a potential therapeutic target for colorectal cancer.
- APC, Adenomatous polyposis coli
- BrdU, bromodeoxyuridine
- ECM, extracellular matrix
- IHC, immunohistochemical analysis
- PCR, polymerase chain reaction
- SPARC, secreted protein acidic, rich in cysteine
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Footnotes
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The corresponding author has the right to grant on behalf of all authors, and does grant on behalf of all authors an exclusive licence (or non-exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd and its Licensees to permit this article to be published in Gut editions and any other BMJPGL products to exploit all subsidiary rights, as set out in our licence http://gut.bmjjournals.com/ifora/licence.pdf
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Grants: This work was funded by Cancer Research UK.
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Conflict of interest: None declared.