title: Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity.
abstract: Given the critical role of tumor O2 delivery in patient prognosis and the rise in preclinical exercise oncology studies, we investigated tumor and host tissue blood flow at rest and during exercise as well as vascular reactivity using a rat prostate cancer model grown in two transplantation sites. In male COP/CrCrl rats, blood flow (via radiolabeled microspheres) to prostate tumors [R3327-MatLyLu cells injected in the left flank (ectopic) or ventral prostate (orthotopic)] and host tissue was measured at rest and during a bout of mild-intensity exercise. α-Adrenergic vasoconstriction to norepinephrine (NE: 10(-9) to 10(-4) M) was determined in arterioles perforating the tumors and host tissue. To determine host tissue exercise hyperemia in healthy tissue, a sham-operated group was included. Blood flow was lower at rest and during exercise in ectopic tumors and host tissue (subcutaneous adipose) vs. the orthotopic tumor and host tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5% (SE), whereas flow to the orthotopic tumor increased by 181 ± 30%. Maximal vasoconstriction to NE was not different between arterioles from either tumor location. However, there was a significantly higher peak vasoconstriction to NE in subcutaneous adipose arterioles (92 ± 7%) vs. prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host tissue blood flow from either location at rest or during exercise. These data demonstrate that blood flow in tumors is dependent on host tissue hemodynamics and that the location of the tumor may critically affect how exercise impacts the tumor microenvironment and treatment outcomes.
authors.affiliation: Department of Kinesiology, Kansas State University, Manhattan, Kansas;
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Garcia
authors.affiliation: Department of Kinesiology, Kansas State University, Manhattan, Kansas; Department of Sports Science, Leipzig University, Leipzig, Germany;
authors.forename: Veronika G C
authors.initials: VG
authors.lastname: Becker
authors.affiliation: Department of Anatomy & Physiology, Edward Via College of Osteopathic Medicine, Auburn Campus, Auburn, Alabama;
authors.forename: Danielle J
authors.initials: DJ
authors.lastname: McCullough
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; and.
authors.forename: John N
authors.initials: JN
authors.lastname: Stabley
authors.affiliation: Department of Kinesiology, Kansas State University, Manhattan, Kansas;
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Gittemeier
authors.affiliation: Department of Kinesiology, Kansas State University, Manhattan, Kansas;
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Opoku-Acheampong
authors.affiliation: Department of Radiation Oncology, University of Florida Health Cancer Center, Gainesville, Florida.
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Sieman
authors.affiliation: Johnson Cancer Research Center, Kansas State University, Manhattan, Kansas; Department of Kinesiology, Kansas State University, Manhattan, Kansas; bjbehnke@ksu.edu.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Behnke
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D006439:Hemodynamics / Q000502:physiology*; D006940:Hyperemia / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D051381:Rats; D012039:Regional Blood Flow / Q000502:physiology*; D012146:Rest / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D009638:Norepinephrine
keywords: blood flow; exercise; prostate cancer; rodent; tumor models