title: A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise.
abstract: 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.
authors.affiliation: Laboratory of Health Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5 Hangi-cho Shimogamo, Sakyo-ku, Kyoto 606-8522, Japan. waoi@koto.kpu-m.ac.jp
authors.forename: Wataru
authors.initials: W
authors.lastname: Aoi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Takagi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tanimura
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Takanami
authors.forename: Yukari
authors.initials: Y
authors.lastname: Kawai
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Sakuma
authors.forename: Liu Po
authors.initials: LP
authors.lastname: Hang
authors.forename: Katsura
authors.initials: K
authors.lastname: Mizushima
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Hirai
authors.forename: Ryota
authors.initials: R
authors.lastname: Koyama
authors.forename: Sayori
authors.initials: S
authors.lastname: Wada
authors.forename: Akane
authors.initials: A
authors.lastname: Higashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D058739:Aberrant Crypt Foci / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015444:Exercise / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D015676:Osteonectin; D010805:Physical Conditioning, Animal / Q000502:physiology; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D015676:Osteonectin; C577241:SPARC protein, human; C578250:SPARC protein, mouse; D025521:Tumor Suppressor Proteins