Decorin, an exercise-induced secretory protein, is associated with improved prognosis in breast cancer patients but does not mediate anti-tumorigenic tissue crosstalk in mice
Purpose: Regular exercise can reduce incidence and progression of breast cancer, but the mechanisms for such effects are not fully understood. The purpose of this study was to examine the mechanisms behind the protective effects of exercise. Methods: We used a variety of rodent and human experimenta...
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2025-12-01
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| author | Marit Hjorth Casey L. Egan Guilherme D. Telles Martin Pal David Gallego-Ortega Oliver K. Fuller Emma D. McLennan Ryan D. Gillis Tae Gyu Oh George E.O. Muscat Surafel Tegegne Michael S.M. Mah Joanna Skhinas Emma Estevez Timothy E. Adams Matthew J. McKay Mark Molloy Kevin I. Watt Hongwei Qian Paul Gregorevic Thomas R. Cox Pernille Hojman Julie Midtgaard Jesper F. Christensen Martin Friedrichsen Renato V. Iozzo Erica K. Sloan Brian G. Drew Jørgen F.P. Wojtaszewski Martin Whitham Mark A. Febbraio |
| author_facet | Marit Hjorth Casey L. Egan Guilherme D. Telles Martin Pal David Gallego-Ortega Oliver K. Fuller Emma D. McLennan Ryan D. Gillis Tae Gyu Oh George E.O. Muscat Surafel Tegegne Michael S.M. Mah Joanna Skhinas Emma Estevez Timothy E. Adams Matthew J. McKay Mark Molloy Kevin I. Watt Hongwei Qian Paul Gregorevic Thomas R. Cox Pernille Hojman Julie Midtgaard Jesper F. Christensen Martin Friedrichsen Renato V. Iozzo Erica K. Sloan Brian G. Drew Jørgen F.P. Wojtaszewski Martin Whitham Mark A. Febbraio |
| author_sort | Marit Hjorth |
| collection | DOAJ |
| description | Purpose: Regular exercise can reduce incidence and progression of breast cancer, but the mechanisms for such effects are not fully understood. The purpose of this study was to examine the mechanisms behind the protective effects of exercise. Methods: We used a variety of rodent and human experimental model systems to determine whether exercise training can reduce tumor burden in breast cancer and to identify mechanism associated with any exercise training effects on tumor burden. Results: We show that voluntary wheel running slows tumor development in the mammary specific polyomavirus middle T antigen overexpression (MMTV-PyMT) mouse model of breast cancer but only when mice are not housed alone. We identify the proteoglycan decorin as a contraction-induced secretory factor that systemically increases in patients with breast cancer immediately following exercise. Moreover, high expression of decorin in tumors is associated with improved prognosis in patients, while treatment of breast cancer cells in vitro with decorin reduces cell proliferation. Notwithstanding, when we overexpressed decorin in murine muscle or injected recombinant decorin systemically into mouse models of breast cancer, elevated plasma decorin concentrations did not result in higher tumor decorin levels and tumor burden was not improved. Conclusion: Exercise training is anti-tumorigenic in a mouse model of luminal breast cancer, but the effect is abrogated by social isolation. The proteoglycan decorin is an exercise-induced secretory protein, and tumor decorin levels are positively associated with improved prognosis in patients. The hypothesis that elevated plasma decorin is a mechanism by which exercise training improves breast cancer progression in humans is not, however, supported by our pre-clinical data since elevated circulating decorin did not increase tumor decorin levels in these models. |
| format | Article |
| id | doaj-art-f8218aacc8854c889c91112d39a38688 |
| institution | Kabale University |
| issn | 2095-2546 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Elsevier |
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| series | Journal of Sport and Health Science |
| spelling | doaj-art-f8218aacc8854c889c91112d39a386882025-01-26T05:03:44ZengElsevierJournal of Sport and Health Science2095-25462025-12-0114100991Decorin, an exercise-induced secretory protein, is associated with improved prognosis in breast cancer patients but does not mediate anti-tumorigenic tissue crosstalk in miceMarit Hjorth0Casey L. Egan1Guilherme D. Telles2Martin Pal3David Gallego-Ortega4Oliver K. Fuller5Emma D. McLennan6Ryan D. Gillis7Tae Gyu Oh8George E.O. Muscat9Surafel Tegegne10Michael S.M. Mah11Joanna Skhinas12Emma Estevez13Timothy E. Adams14Matthew J. McKay15Mark Molloy16Kevin I. Watt17Hongwei Qian18Paul Gregorevic19Thomas R. Cox20Pernille Hojman21Julie Midtgaard22Jesper F. Christensen23Martin Friedrichsen24Renato V. Iozzo25Erica K. Sloan26Brian G. Drew27Jørgen F.P. Wojtaszewski28Martin Whitham29Mark A. Febbraio30Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo 0317, Norway; Garvan Institute of Medical Research, Sydney, NSW 2010, AustraliaDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, AustraliaDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia; Laboratory of Neuromuscular Adaptations to Strength Training, School of Physical Education and Sport, University of São Paulo (USP), São Paulo 05508-030, Brazil; Center of Study in Exercise and Oncology (CEEO), Campinas 13083-888, BrazilGarvan Institute of Medical Research, Sydney, NSW 2010, Australia; School of Dentistry & Medical Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, AustraliaSchool of Biomedical Engineering, University of Technology, Sydney, NSW 2678, AustraliaDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, AustraliaDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, AustraliaDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, AustraliaCollege of Medicine, University of Oklahoma, Oklahoma City, OK 73117, USA; Institute of Molecular Biosciences, University of Queensland, St. Lucia, QLD 4072, AustraliaInstitute of Molecular Biosciences, University of Queensland, St. Lucia, QLD 4072, AustraliaDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, AustraliaDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, AustraliaGarvan Institute of Medical Research, Sydney, NSW 2010, AustraliaGarvan Institute of Medical Research, Sydney, NSW 2010, AustraliaCSIRO Manufacturing, Clayton, VIC 3168, AustraliaAustralian Proteome Analysis Facility, Macquarie University, Sydney, NSW 2109, Australia; School of Medical Sciences, University of Sydney, Sydney, NSW 2050, AustraliaAustralian Proteome Analysis Facility, Macquarie University, Sydney, NSW 2109, Australia; School of Medical Sciences, University of Sydney, Sydney, NSW 2050, AustraliaMurdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, VIC 3053, Australia; Department of Physiology, The University of Melbourne, Melbourne, VIC 3052, AustraliaDepartment of Physiology, The University of Melbourne, Melbourne, VIC 3052, AustraliaDepartment of Physiology, The University of Melbourne, Melbourne, VIC 3052, AustraliaGarvan Institute of Medical Research, Sydney, NSW 2010, AustraliaCopenhagen University Hospital, Copenhagen 2100, DenmarkCopenhagen University Hospital, Copenhagen 2100, DenmarkCopenhagen University Hospital, Copenhagen 2100, DenmarkDepartment of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen 2100, DenmarkSidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19144, USADrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, AustraliaBaker Heart and Diabetes Institute, Prahran, VIC 3004, AustraliaDepartment of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen 2100, DenmarkSchool of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Edgbaston B15 2TT, UK; Corresponding authors.Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia; Corresponding authors.Purpose: Regular exercise can reduce incidence and progression of breast cancer, but the mechanisms for such effects are not fully understood. The purpose of this study was to examine the mechanisms behind the protective effects of exercise. Methods: We used a variety of rodent and human experimental model systems to determine whether exercise training can reduce tumor burden in breast cancer and to identify mechanism associated with any exercise training effects on tumor burden. Results: We show that voluntary wheel running slows tumor development in the mammary specific polyomavirus middle T antigen overexpression (MMTV-PyMT) mouse model of breast cancer but only when mice are not housed alone. We identify the proteoglycan decorin as a contraction-induced secretory factor that systemically increases in patients with breast cancer immediately following exercise. Moreover, high expression of decorin in tumors is associated with improved prognosis in patients, while treatment of breast cancer cells in vitro with decorin reduces cell proliferation. Notwithstanding, when we overexpressed decorin in murine muscle or injected recombinant decorin systemically into mouse models of breast cancer, elevated plasma decorin concentrations did not result in higher tumor decorin levels and tumor burden was not improved. Conclusion: Exercise training is anti-tumorigenic in a mouse model of luminal breast cancer, but the effect is abrogated by social isolation. The proteoglycan decorin is an exercise-induced secretory protein, and tumor decorin levels are positively associated with improved prognosis in patients. The hypothesis that elevated plasma decorin is a mechanism by which exercise training improves breast cancer progression in humans is not, however, supported by our pre-clinical data since elevated circulating decorin did not increase tumor decorin levels in these models.http://www.sciencedirect.com/science/article/pii/S2095254624001480Breast cancerExercise trainingMuscle secretory factorsProteoglycans |
| spellingShingle | Marit Hjorth Casey L. Egan Guilherme D. Telles Martin Pal David Gallego-Ortega Oliver K. Fuller Emma D. McLennan Ryan D. Gillis Tae Gyu Oh George E.O. Muscat Surafel Tegegne Michael S.M. Mah Joanna Skhinas Emma Estevez Timothy E. Adams Matthew J. McKay Mark Molloy Kevin I. Watt Hongwei Qian Paul Gregorevic Thomas R. Cox Pernille Hojman Julie Midtgaard Jesper F. Christensen Martin Friedrichsen Renato V. Iozzo Erica K. Sloan Brian G. Drew Jørgen F.P. Wojtaszewski Martin Whitham Mark A. Febbraio Decorin, an exercise-induced secretory protein, is associated with improved prognosis in breast cancer patients but does not mediate anti-tumorigenic tissue crosstalk in mice Journal of Sport and Health Science Breast cancer Exercise training Muscle secretory factors Proteoglycans |
| title | Decorin, an exercise-induced secretory protein, is associated with improved prognosis in breast cancer patients but does not mediate anti-tumorigenic tissue crosstalk in mice |
| title_full | Decorin, an exercise-induced secretory protein, is associated with improved prognosis in breast cancer patients but does not mediate anti-tumorigenic tissue crosstalk in mice |
| title_fullStr | Decorin, an exercise-induced secretory protein, is associated with improved prognosis in breast cancer patients but does not mediate anti-tumorigenic tissue crosstalk in mice |
| title_full_unstemmed | Decorin, an exercise-induced secretory protein, is associated with improved prognosis in breast cancer patients but does not mediate anti-tumorigenic tissue crosstalk in mice |
| title_short | Decorin, an exercise-induced secretory protein, is associated with improved prognosis in breast cancer patients but does not mediate anti-tumorigenic tissue crosstalk in mice |
| title_sort | decorin an exercise induced secretory protein is associated with improved prognosis in breast cancer patients but does not mediate anti tumorigenic tissue crosstalk in mice |
| topic | Breast cancer Exercise training Muscle secretory factors Proteoglycans |
| url | http://www.sciencedirect.com/science/article/pii/S2095254624001480 |
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