Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity
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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.
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Preclinical studies show that tumor perfusion and oxygenation rise from the first exercise session.
“Preclinical studies indicate that tumor perfusion and oxygenation increase from the very first exercise session (5,9,11).”
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- Authors
- Garcia, E., Becker, V. G. C., McCullough, D. J., Stabley, J. N., Gittemeier, E. M., Opoku-Acheampong, A. B., Sieman, D. W., & Behnke, B. J.
- Affiliations
- Kansas State University (US)
- Edward Via College of Osteopathic Medicine (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Behnke, Bradley J.
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 2016-04-28
- Volume
- 121
- Issue
- 1
- Pages
- 15-24
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- PMC
- PMC4967242
- OpenAlex
- W2343432965
- Cited by
- 57
- References
- 63
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 2 · 2023: 8 · 2022: 5 · 2021: 8 · 2020: 7 · 2019: 3 · 2018: 5 · 2017: 5 · 2016: 2
- FWCI
- 10.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Cancer Society (ACS) (RSG-14-150-01-CCE)
- HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI) (1 R25 HL115473-01)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- prostate cancer, tumor perfusion, exercise hyperemia, ectopic tumor, orthotopic tumors, vascular reactivity, norepinephrine-induced vasoconstriction, tumor microenvironment, exercise oncology, subcutaneous adipose tissue, arterioles
- MeSH terms
- Animals, Arterioles, Hemodynamics, Hyperemia, Male, Norepinephrine, Physical Conditioning, Animal, Prostatic Neoplasms, Regional Blood Flow, Rest, Vasoconstriction, Vasoconstrictor Agents, Cell Line, Tumor, Rats
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