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...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.展开更多
Obesity has been linked to a range of pathologies,including dementia.In contrast,regular physical activity is associated with the prevention or reduced progression of neurodegeneration.Specifically,physical activity c...Obesity has been linked to a range of pathologies,including dementia.In contrast,regular physical activity is associated with the prevention or reduced progression of neurodegeneration.Specifically,physical activity can improve memory and spatial cognition,reduce age-related cognitive decline,and preserve brain volume,but the mechanisms are not fully understood.Accordingly,we investigated whether any detrimental effects of high-fat diet(HFD)-induced obesity on cognition,motor behavior,adult hippocampal neurogenesis,and brain-derived neurotrophic factor(BDNF)could be mitigated by voluntary exercise training in male C57Bl/6 mice.HFD-induced impairment of motor function was not reversed by exercise.Importantly,voluntary wheel running improved long-term memory and increased hippocampal neurogenesis,suggesting that regular physical activity may prevent cognitive decline in obesity.展开更多
基金supported by an NHMRC Investigator Grant (APP1194141)supported by project grants from the NHMRC (APP1042465, APP1041760, and APP1156511)。
文摘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.
基金supported by an NHMRC Investigator Grant(APP1194141)supported by project grants from the NHMRC(APP1042465,APP1041760,and APP1156511).
文摘Obesity has been linked to a range of pathologies,including dementia.In contrast,regular physical activity is associated with the prevention or reduced progression of neurodegeneration.Specifically,physical activity can improve memory and spatial cognition,reduce age-related cognitive decline,and preserve brain volume,but the mechanisms are not fully understood.Accordingly,we investigated whether any detrimental effects of high-fat diet(HFD)-induced obesity on cognition,motor behavior,adult hippocampal neurogenesis,and brain-derived neurotrophic factor(BDNF)could be mitigated by voluntary exercise training in male C57Bl/6 mice.HFD-induced impairment of motor function was not reversed by exercise.Importantly,voluntary wheel running improved long-term memory and increased hippocampal neurogenesis,suggesting that regular physical activity may prevent cognitive decline in obesity.
