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Deficiency of SPARC suppresses intestinal tumorigenesis in APCMin/+ mice

Sansom, Owen J., Mansergh, Fiona Catherine, Evans, Martin John, Wilkins, Julie and Clarke, Alan Richard 2007. Deficiency of SPARC suppresses intestinal tumorigenesis in APCMin/+ mice. Gut 56 , pp. 1410-1414. 10.1136/gut.2006.116921

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
ISSN: 0017-5749
Last Modified: 01 Feb 2020 23:15

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