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.
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Exercise restrains tumor growth and improves immune checkpoint inhibitor efficacy in multiple preclinical cancer models.
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Exercise has potent antitumor effects in preclinical models and cancer patients.
“Exercise exerts potent antitumor effects in both preclinical models5,8–13 and cancer patients6.”
From Exercise-induced microbiota metabolite enhances CD8 T cell antitumor immunity promoting immunotherapy efficacy (2025) · cites this paper as [9]
A few mechanistic studies have demonstrated a potential role of other myokines, including Oncostatin M, irisin, and SPARC in the suppression of breast and colon cancer growth.
“A few mechanistic studies have demonstrated a potential role of other myokines, including Oncostatin M, irisin, and SPARC in the suppression of breast and colon cancer growth (41, 224-227).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [225]
SPARC regulates cell function and tissue remodelling and inhibits proliferation while promoting apoptosis in a mouse colon cancer cell line.
“this matricellular protein regulates cell function and tissue remodelling, while inhibiting proliferation and promoting apoptosis of a mouse colon cancer cell line132.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [132]
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“com/edrv A few mechanistic studies have demonstrated a potential role of other myokines, including Oncostatin M, irisin, and SPARC in the suppression of breast and colon cancer growth (41, 224-227).”
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“Regarding AE, most of the studies included had an exercise duration of 30 (cid:1) 60 min with intensity from 50% to 70% VO 2max or 60% HR reserve using MICAE (Supplementary Table 1), 52,53,75,79,93,104 which appears sufficient to drive alterations in SPARC levels.”
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- Authors
- Aoi, W., Naito, Y., Takagi, T., Tanimura, Y., Takanami, Y., Kawai, Y., Sakuma, K., Hang, L. P., Mizushima, K., Hirai, Y., Koyama, R., Wada, S., Higashi, A., Kokura, S., Ichikawa, H., & Yoshikawa, T.
- Affiliations
- Kyoto Prefectural University (JP)
- Kyoto Prefectural University of Medicine (JP)
- Otsuma Women's University (JP)
- Louis Pasteur Center for Medical Research (JP)
- Toyohashi University of Technology (JP)
- Doshisha University (JP)
- Corresponding author
- Aoi, Wataru
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2012-07-31
- Volume
- 62
- Issue
- 6
- Pages
- 882-889
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2153409078
- Cited by
- 347
- References
- 42
- Citations by year
- 2026: 23 · 2025: 24 · 2024: 31 · 2023: 31 · 2022: 42 · 2021: 32 · 2020: 37 · 2019: 21 · 2018: 17 · 2017: 23 · 2016: 23 · 2015: 15 · 2014: 13 · 2013: 12 · 2012: 1
- FWCI
- 13.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Scheme for Promotion of Academic and Research Collaboration
- Japan Society for the Promotion of Science (22590705, 22590706)
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Keywords
- SPARC, myokines, physical activity, colon tumorigenesis, colon cancer prevention, apoptosis, caspase-3, caspase-8, skeletal muscle, aberrant crypt foci, azoxymethane-induced colon cancer, cyclic strain
- MeSH terms
- Animals, Cell Transformation, Neoplastic, Colonic Neoplasms, Glycoproteins, Humans, Male, Mice, Inbred ICR, Physical Conditioning, Animal, Tumor Cells, Cultured, Exercise, Osteonectin, Apoptosis, Mice, Knockout, Muscle Fibers, Skeletal, Oligonucleotide Array Sequence Analysis, Tumor Suppressor Proteins, Mice, Aberrant Crypt Foci
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