Blood flow responses to mild-intensity exercise in ectopic versus orthotopic prostate tumors; dependence upon host-tissue hemodynamics and vascular reactivity.

Given the critical role of tumor O2 delivery on 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.

METHODS - 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. Alpha-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.

RESULTS - Blood flow was lower at rest and during exercise in ectopic tumors and host-tissue (subcutaneous adipose) versus the orthotopic tumor and host-tissue (prostate). During exercise, blood flow to the ectopic tumor significantly decreased by 25 ± 5%, 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%) versus prostate arterioles (55 ± 7%). Establishment of the tumor did not alter host-tissue blood flow from either location at rest or during exercise.

CONCLUSIONS - These data demonstrate 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.

Journal of applied physiology (Bethesda, Md. : 1985). 2016 Apr 28 [Epub ahead of print]

Emmanuel Garcia, Veronika G C Becker, Danielle J McCullough, John N Stabley, Elizabeth M Gittemeier, Alexander B Opoku-Acheampong, Dietmar W Siemann, Bradley Jon Behnke

Kansas State University., Kansas State University., Edward Via College of Osteopathic Medicine, Auburn Campus., University of Texas Southwestern Medical Center., Kansas State University., Kansas State University., University of Florida., Kansas State University.