PMID- 29357514
OWN - NLM
STAT- MEDLINE
DCOM- 20191107
LR  - 20191210
IS  - 1522-1601 (Electronic)
IS  - 0161-7567 (Linking)
VI  - 124
IP  - 4
DP  - 2018 Apr 1
TI  - Voluntary exercise slows breast tumor establishment and reduces tumor hypoxia in 
      ApoE(-/-) mice.
PG  - 938-949
LID - 10.1152/japplphysiol.00738.2017 [doi]
AB  - Exercise reduces the risk of breast cancer development and improves survival in 
      breast cancer patients. However, the underlying mechanisms of this protective 
      effect remain to be fully elucidated, and it is unclear whether exercise can 
      attenuate the protumor effects of obesity and related hyperlipidemia on breast 
      cancer growth and development. We hypothesized that exercise attenuates the 
      negative effect of hyperlipidemia through normalization of the tumor 
      microenvironment and improved T cell infiltrate. Hyperlipidemic ApoE(-/-) mice 
      with orthotopic EO771 breast tumors were randomly assigned to one of two 
      voluntary running groups or sedentary controls, and muscular cytochrome c oxidase 
      subunit IV (COX-IV) expression was used as a biomarker for the level of exercise. 
      Tumors from mice with high muscular COX-IV expression took significantly longer 
      to reach 100 mm(3) ( P = 0.008), but showed no difference in growth rate once the 
      tumor was established. Wheel running appeared to reduce internal metastases, but 
      did not affect T cell infiltrate or the proportion of regulatory and cytotoxic T 
      cells within the tumor. Serum levels of monocyte chemoattractant protein-1 
      (MCP-1) were significantly increased by tumor burden ( P = 0.02) and correlated 
      with spleen weight ( P < 0.0001, R = 0.65). Furthermore, tumor hypoxia was 
      significantly decreased in mice with high muscular COX-IV expression ( P = 0.01). 
      Taken together, these results indicate that wheel running can slow the 
      establishment of primary and secondary EO771 breast tumors and induce beneficial 
      changes in the breast tumor microenvironment in ApoE(-/-) mice. NEW & NOTEWORTHY 
      In this first study to investigate the effect of exercise on tumor behavior in a 
      hyperlipidemic model, we hypothesized that wheel running would counteract the 
      protumorigenic environment generated by hyperlipidemia. Wheel running slowed 
      establishment of primary and secondary tumors and reduced tumor hypoxia but did 
      not affect exponential tumor growth in ApoE(-/-) mice. Overall, voluntary wheel 
      running induced favorable microenvironmental changes in breast tumors.
FAU - Buss, Linda A
AU  - Buss LA
AD  - Mackenzie Cancer Research Group, Department of Pathology, University of Otago , 
      Christchurch , New Zealand.
FAU - Dachs, Gabi U
AU  - Dachs GU
AD  - Mackenzie Cancer Research Group, Department of Pathology, University of Otago , 
      Christchurch , New Zealand.
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171214
PL  - United States
TA  - J Appl Physiol (1985)
JT  - Journal of applied physiology (Bethesda, Md. : 1985)
JID - 8502536
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/etiology/*prevention & control
MH  - Female
MH  - Hyperlipidemias/complications
MH  - Hypoxia/prevention & control
MH  - Mice, Knockout, ApoE
MH  - *Motor Activity
MH  - Neoplasm Transplantation
MH  - *Physical Conditioning, Animal
MH  - *Tumor Microenvironment
OTO - NOTNLM
OT  - breast cancer
OT  - hyperlipidemia
OT  - hypoxia
OT  - physical activity
OT  - tumor microenvironment
EDAT- 2018/01/24 06:00
MHDA- 2019/11/08 06:00
CRDT- 2018/01/24 06:00
PHST- 2018/01/24 06:00 [pubmed]
PHST- 2019/11/08 06:00 [medline]
PHST- 2018/01/24 06:00 [entrez]
AID - 10.1152/japplphysiol.00738.2017 [doi]
PST - ppublish
SO  - J Appl Physiol (1985). 2018 Apr 1;124(4):938-949. doi: 
      10.1152/japplphysiol.00738.2017. Epub 2017 Dec 14.