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Deficiency of SPARC suppresses intestinal tumourigenesis in APCMin/+ Mice
  1. Owen James Sansom (o.sansom{at}beatson.gla.ac.uk)
  1. Beatson Institute for Cancer Research, United Kingdom
    1. Fiona Mansergh (manserghfc{at}cardiff.ac.uk)
    1. University of Cardiff, United Kingdom
      1. Martin Evans (evansmj{at}cardiff.ac.uk)
      1. University of Cardiff, United Kingdom
        1. Julie Wilkins (j.wilkins{at}beatson.gla.ac.uk)
        1. Beatson Institute for Cancer Research, United Kingdom
          1. Alan Clarke (clarkear{at}cf.ac.uk)
          1. University of Cardiff, United Kingdom

            Abstract

            Background and Aims SPARC (Secreted protein acidic, rich in cysteine) is a matricellular protein which has 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 tumourigenesis in vivo.

            Methods. SPARC upregulation was determined in intestinal adenomas of tumour prone ApcMin/+ mice at both the RNA and protein level. To determine the functional importance of SPARC for intestinal tumourigenesis we then intercrossed Sparc knockout mice with ApcMin/+ mice (n=20). Intestinal enterocyte migration was examined using BrdU labelling studies.

            Results Levels of murine Sparc and several related proteins were upregulated in adenomas arising in ApcMin/+ mice. Deficiency of Sparc strongly suppressed adenoma formation in ApcMin/+ mice (p=>0.0001). Importantly 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
            • Colorectal Cancer
            • Mouse model
            • SPARC

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