Deficiency of SPARC suppresses intestinal tumorigenesis in APCMin/+ mice. Issue 10 (13th February 2007)

• Record Type: Journal Article
• Authors: Sansom, Owen J; Mansergh, Fiona C; Evans, Martin J; Wilkins, Julie A; Clarke, Alan R
• Is Part Of: Gut. Volume 56:Issue 10(2007)
• Page Start: 1410
• Page End: 1414
• Publication Date: 2007-02-13
• Subjects: APC, Adenomatous polyposis coli -- BrdU, bromodeoxyuridine -- ECM, extracellular matrix -- IHC, immunohistochemical analysis -- PCR, polymerase chain reaction -- SPARC, secreted protein acidic, rich in cysteine; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.2006.116921
• Languages: English
• ISSNs: 0017-5749

Abstract

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 Apc Min/+ 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 Apc Min/+ 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 Apc Min/+ mice. A deficiency of Sparc strongly suppressed adenoma formation in Apc Min/+ 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.