Document Detail

Exercise modulation of the host-tumor interaction in an orthotopic model of murine prostate cancer.
MedLine Citation:
PMID:  22604887     Owner:  NLM     Status:  MEDLINE    
The purpose of this study is to investigate the effects of exercise on cancer progression, metastasis, and underlying mechanisms in an orthotopic model of murine prostate cancer. C57BL/6 male mice (6-8 wk of age) were orthotopically injected with transgenic adenocarcinoma of mouse prostate C-1 cells (5 × 10(5)) and randomly assigned to exercise (n = 28) or a non-intervention control (n = 31) groups. The exercise group was given voluntary access to a wheel 24 h/day for the duration of the study. Four mice per group were serially killed on days 14, 31, and 36; the remaining 38 mice (exercise, n = 18; control, n = 20) were killed on day 53. Before death, MRI was performed to assess tumor blood perfusion. Primary tumor growth rate was comparable between groups, but expression of prometastatic genes was significantly modulated in exercising animals with a shift toward reduced metastasis. Exercise was associated with increased activity of protein kinases within the MEK/MAPK and PI3K/mTOR signaling cascades with subsequent increased intratumoral protein levels of HIF-1α and VEGF. This was associated with improved tumor vascularization. Multiplex ELISAs revealed distinct reductions in plasma concentrations of several angiogenic cytokines in the exercise group, which was associated with increased expression of angiogenic and metabolic genes in the skeletal muscle. Exercise-induced stabilization of HIF-1α and subsequent upregulation of VEGF was associated with "productive" tumor vascularization with a shift toward suppressed metastasis in an orthotopic model of prostate cancer.
Lee W Jones; Jodi Antonelli; Elizabeth M Masko; Gloria Broadwater; Christopher D Lascola; Diane Fels; Mark W Dewhirst; Jason R B Dyck; Jeevan Nagendran; Catherine T Flores; Allison S Betof; Erik R Nelson; Michael Pollak; Rajesh C Dash; Martin E Young; Stephen J Freedland
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-17
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  113     ISSN:  1522-1601     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-20     Completed Date:  2012-12-18     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  263-72     Citation Subset:  IM    
Duke University Medical Center, Durham, NC 27710, USA.
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MeSH Terms
Adenocarcinoma / physiopathology*,  prevention & control,  secondary*
Cytokines / blood*
Exercise Therapy / methods*
Mice, Inbred C57BL
Neoplasms, Experimental
Neovascularization, Pathologic / physiopathology*,  prevention & control
Physical Conditioning, Animal / methods*
Prostatic Neoplasms / physiopathology*,  prevention & control,  secondary
Treatment Outcome
Grant Support
CA125458/CA/NCI NIH HHS; CA133895/CA/NCI NIH HHS; CA138634/CA/NCI NIH HHS; CA142566/CA/NCI NIH HHS; CA143254/CA/NCI NIH HHS; //Canadian Institutes of Health Research
Reg. No./Substance:

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