title: Exercise modulation of the host-tumor interaction in an orthotopic model of murine prostate cancer.
abstract: 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.
authors.affiliation: Duke University Medical Center, Durham, NC 27710, USA. lee.w.jones@duke.edu
authors.forename: Lee W
authors.initials: LW
authors.lastname: Jones
authors.forename: Jodi
authors.initials: J
authors.lastname: Antonelli
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Masko
authors.forename: Gloria
authors.initials: G
authors.lastname: Broadwater
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Lascola
authors.forename: Diane
authors.initials: D
authors.lastname: Fels
authors.forename: Mark W
authors.initials: MW
authors.lastname: Dewhirst
authors.forename: Jason R B
authors.initials: JR
authors.lastname: Dyck
authors.forename: Jeevan
authors.initials: J
authors.lastname: Nagendran
authors.forename: Catherine T
authors.initials: CT
authors.lastname: Flores
authors.forename: Allison S
authors.initials: AS
authors.lastname: Betof
authors.forename: Erik R
authors.initials: ER
authors.lastname: Nelson
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.forename: Rajesh C
authors.initials: RC
authors.lastname: Dash
authors.forename: Martin E
authors.initials: ME
authors.lastname: Young
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Freedland
mesh_terms: D000230:Adenocarcinoma / Q000503:physiopathology* / Q000517:prevention & control / Q000556:secondary*; D000818:Animals; D016207:Cytokines / Q000097:blood*; D005081:Exercise Therapy / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental; D009389:Neovascularization, Pathologic / Q000503:physiopathology* / Q000517:prevention & control; D010805:Physical Conditioning, Animal / Q000379:methods*; D011471:Prostatic Neoplasms / Q000503:physiopathology* / Q000517:prevention & control / Q000556:secondary; D016896:Treatment Outcome
chemical_list: D016207:Cytokines