RT Journal Article
SR Electronic
T1 A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 882
OP 889
DO 10.1136/gutjnl-2011-300776
VO 62
IS 6
A1 Wataru Aoi
A1 Yuji Naito
A1 Tomohisa Takagi
A1 Yuko Tanimura
A1 Yoshikazu Takanami
A1 Yukari Kawai
A1 Kunihiro Sakuma
A1 Liu Po Hang
A1 Katsura Mizushima
A1 Yasuko Hirai
A1 Ryota Koyama
A1 Sayori Wada
A1 Akane Higashi
A1 Satoshi Kokura
A1 Hiroshi Ichikawa
A1 Toshikazu Yoshikawa
YR 2013
UL http://gut.bmj.com/content/62/6/882.abstract
AB Objective Several epidemiological studies have shown that regular exercise can prevent the onset of colon cancer, although the underlying mechanism is unclear. Myokines are secreted skeletal muscle proteins responsible for some exercise-induced health benefits including metabolic improvement and anti-inflammatory effects in organs. The purpose of this study was to identify new myokines that contribute to the prevention of colon tumorigenesis. Methods To identify novel secreted muscle-derived proteins, DNA microarrays were used to compare the transcriptome of muscle tissue in sedentary and exercised young and old mice. The level of circulating secreted protein acidic and rich in cysteine (SPARC) was measured in mice and humans that performed a single bout of exercise. The effect of SPARC on colon tumorigenesis was examined using SPARC-null mice. The secretion and function of SPARC was examined in culture experiments. Results A single bout of exercise increased the expression and secretion of SPARC in skeletal muscle in both mice and humans. In addition, in an azoxymethane-induced colon cancer mouse model, regular low-intensity exercise significantly reduced the formation of aberrant crypt foci in wild-type mice but not in SPARC-null mice. Furthermore, regular exercise enhanced apoptosis in colon mucosal cells and increased the cleaved forms of caspase-3 and caspase-8 in wild-type mice but not in SPARC-null mice. Culture experiments showed that SPARC secretion from myocytes was induced by cyclic stretch and inhibited proliferation with apoptotic effect of colon cancer cells. Conclusions These findings suggest that exercise stimulates SPARC secretion from muscle tissues and that SPARC inhibits colon tumorigenesis by increasing apoptosis.