Deficiency of SPARC suppresses intestinal tumorigenesis in APCMin/+ mice.
OBJECTIVE
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>or=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.
Sansom
Owen J
OJ
Beatson Institute of Cancer Research, Glasgow, Scotland, UK. o.sansom@beaston.gla.ac.uk
Mansergh
Fiona C
FC
Evans
Martin J
MJ
Wilkins
Julie A
JA
Clarke
Alan R
AR
D000230:Adenocarcinoma / Q000378:metabolism; D000236:Adenoma / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism; D004195:Disease Models, Animal; D020895:Enterocytes / Q000502:physiology; D007414:Intestinal Neoplasms / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000172:deficiency* / Q000378:metabolism; D015676:Osteonectin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D015854:Up-Regulation
D009363:Neoplasm Proteins; D015676:Osteonectin; D012333:RNA, Messenger; D012334:RNA, Neoplasm