Tumor arteriolar function in a novel orthotopic model of breast cancer

• Published in: Physiology (Bethesda, Md.) Md.), 2023-05, Vol.38 (S1)
• Main Authors: Kunkel, Olivia, Horn, Andrew, Behnke, Brad
• Format: Article
• Language: English
• ISSN: 1548-9213; 1548-9221
• DOI: 10.1152/physiol.2023.38.S1.5795067

Abstract only Introduction: For women in the United States, breast cancer is the most diagnosed non-skin cancer and second leading cause of cancer-related deaths. While the overall 5-year survival rate of all stages of breast cancer is 90%, several features of the tumor microenvironment contribute to an individual patient’s treatment success. The efficacy of radiation is dependent upon the presence of oxygen, and many solid tumors are hypoxic. In addition to its effect on treatment success, tumor hypoxia also leads to a more aggressive phenotype and increases metastatic potential. Therefore, improving tumor blood flow and thus, hypoxia, may improve the efficacy of radiation as well as reduce metastatic potential. The purpose of this study was to understand the vasomotor function of arterioles from orthotopic breast tumors to determine the potential mechanisms to improve tumor blood flow. Methods: Female Fischer 344 (retired breeder) rats were randomly assigned to non-tumor control (CON; n=4) and tumor bearing (TB; n=6) groups. TB rats were injected with 3x103 Mat B III cells into the mammary duct. Once tumors reached 10-15 mm in diameter, rats were euthanized and tumor feed arterioles were harvested. Blood vessels from CON rats were harvested from the mammary tissue. Vessels were cannulated on glass micro-pipettes, pressurized at 90 cmH 2 O, and allowed to equilibrate for one hour. Alpha (α)-adrenergic and myogenic contractile responses were assessed and vessel diameter recorded. Data were analyzed using a Two-Way Repeated Measures ANOVA and determined to be significant if p ≤ 0.05. Results: There were no differences between groups in α-adrenergic vasoconstriction or between active and passive pressure-diameter responses. There was no difference in maximal constriction to norepinephrine for CON vs. TB (53.07 ± 19.4% vs. 40.68 ± 13.9%) or maximal pressure-induced constriction (myogenic response) for CON vs. TB (11.2 ± 2.6% vs. 13.03 ± 5.0%). Conclusions: The vascular bed of rodent mammary tumors may be unique given that, unlike other solid tumor arterioles (i.e. prostate), breast tumor arterioles do not exhibit significant impairments in contractile response to norepinephrine or in myogenic vasoconstriction. Further investigation is needed to determine the vascular response to other stimuli (flow, bradykinin, etc.) and to quantify tumor hypoxia, but tumor blood flow may depend more heavily on vessel patency and vascular density than on the functional nature