Murine breast cancer feed arteries are thin-walled with reduced α1A-adrenoceptor expression and attenuated sympathetic vasocontraction
| Autor: | Anne Sofie Froelunde, Ebbe Boedtkjer, Sukhan Kim, Kristoffer B Hansen, Nicolai Jessen, Marit Edna Ohlenbusch |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Vascular smooth muscle Angiogenesis Receptor ErbB-2 Receptor expression Sympathetic nerve activity Breast Neoplasms Mammary Neoplasms Animal 030204 cardiovascular system & hematology lcsh:RC254-282 Membrane Potentials 03 medical and health sciences Mice Norepinephrine 0302 clinical medicine Breast cancer Internal medicine Receptors Adrenergic alpha-1 Prazosin medicine Animals Humans Adrenergic receptors RNA Messenger Electrical impedance myography Neovascularization Pathologic Chemistry Myography Cancer Arteries Arterial structure medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Gene Expression Regulation Neoplastic Oxygen 030104 developmental biology Endocrinology Tumor microenvironment Cancer cell Adrenergic alpha-1 Receptor Antagonists Calcium Female medicine.drug Research Article Muscle Contraction |
| Zdroj: | Breast Cancer Research, Vol 20, Iss 1, Pp 1-12 (2018) Breast Cancer Research : BCR Frølunde, A S, Ohlenbusch, M E, Berg-Hansen, K, Jessen, N, Kim, S & Boedtkjer, E 2018, ' Murine breast cancer feed arteries are thin-walled with reduced α 1A-adrenoceptor expression and attenuated sympathetic vasocontraction ', Breast Cancer Research, vol. 20, 20 . https://doi.org/10.1186/s13058-018-0952-8 |
| Popis: | Background Perfusion of breast cancer tissue limits oxygen availability and metabolism but angiogenesis inhibitors have hitherto been unsuccessful for breast cancer therapy. In order to identify abnormalities and possible therapeutic targets in mature cancer arteries, we here characterize the structure and function of cancer feed arteries and corresponding control arteries from female FVB/N mice with ErbB2-induced breast cancer. Methods We investigated the contractile function of breast cancer feed arteries and matched control arteries by isometric myography and evaluated membrane potentials and intracellular [Ca2+] using sharp electrodes and fluorescence microscopy, respectively. Arterial wall structure is assessed by transmission light microscopy of arteries mounted in wire myographs and by evaluation of histological sections using the unbiased stereological disector technique. We determined the expression of messenger RNA by reverse transcription and quantitative polymerase chain reaction and studied receptor expression by confocal microscopy of arteries labelled with the BODIPY-tagged α1-adrenoceptor antagonist prazosin. Results Breast cancer feed arteries are thin-walled and produce lower tension than control arteries of similar diameter in response to norepinephrine, thromboxane-analog U46619, endothelin-1, and depolarization with elevated [K+]. Fewer layers of similarly-sized vascular smooth muscle cells explain the reduced media thickness of breast cancer arteries. Evidenced by lower media stress, norepinephrine-induced and thromboxane-induced tension development of breast cancer arteries is reduced more than is explained by the thinner media. Conversely, media stress during stimulation with endothelin-1 and elevated [K+] is similar between breast cancer and control arteries. Correspondingly, vascular smooth muscle cell depolarizations and intracellular Ca2+ responses are attenuated in breast cancer feed arteries during norepinephrine but not during endothelin-1 stimulation. Protein expression of α1-adrenoceptors and messenger RNA levels for α1A-adrenoceptors are lower in breast cancer arteries than control arteries. Sympathetic vasocontraction elicited by electrical field stimulation is inhibited by α1-adrenoceptor blockade and reduced in breast cancer feed arteries compared to control arteries. Conclusion Thinner media and lower α1-adrenoceptor expression weaken contractions of breast cancer feed arteries in response to sympathetic activity. We propose that abnormalities in breast cancer arteries can be exploited to modify tumor perfusion and thereby either starve cancer cells or facilitate drug and oxygen delivery during chemotherapy or radiotherapy. Electronic supplementary material The online version of this article (10.1186/s13058-018-0952-8) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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