TY - JOUR
T1 - Bronchial artery angiogenesis drives lung tumor growth
AU - Eldridge, Lindsey
AU - Moldobaeva, Aigul
AU - Zhong, Qiong
AU - Jenkins, John
AU - Snyder, Michael
AU - Brown, Robert H.
AU - Mitzner, Wayne
AU - Wagner, Elizabeth M.
N1 - Publisher Copyright:
©2016 AACR.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/10/15
Y1 - 2016/10/15
N2 - Angiogenesis is vital for tumor growth but in well-vascularized organs such as the lung its importance is unclear. This situation is complicated by the fact that the lung has two separate circulations, the pulmonary and the systemic bronchial circulation. There are few relevant animal models of non-small cell lung cancer, which can be used to study the lung's complex circulations, and mice, lacking a systemic bronchial circulation cannot be used. We report here a novel orthotopic model of non-small cell lung cancer in rats, where we have studied the separate contributions of each of the two circulations for lung tumor growth. Results show that bronchial artery perfusion, quantified by fluorescent microspheres (206% increase in large tumors) or high-resolution computed tomography scans (276% increase in large tumors), parallels the growth in tumor volume, whereas pulmonary artery perfusion remained unchanged. Ablation of the bronchial artery after the initiation of tumor growth resulted in a decrease in tumor volume over a subsequent course of 4 weeks. These results demonstrate that although the existing pulmonary circulation can supply the metabolic needs for tumor initiation, further growth of the tumor requires angiogenesis from the highly proliferative bronchial circulation. This model may be useful to investigate new therapeutic approaches that target specifically the bronchial circulation.
AB - Angiogenesis is vital for tumor growth but in well-vascularized organs such as the lung its importance is unclear. This situation is complicated by the fact that the lung has two separate circulations, the pulmonary and the systemic bronchial circulation. There are few relevant animal models of non-small cell lung cancer, which can be used to study the lung's complex circulations, and mice, lacking a systemic bronchial circulation cannot be used. We report here a novel orthotopic model of non-small cell lung cancer in rats, where we have studied the separate contributions of each of the two circulations for lung tumor growth. Results show that bronchial artery perfusion, quantified by fluorescent microspheres (206% increase in large tumors) or high-resolution computed tomography scans (276% increase in large tumors), parallels the growth in tumor volume, whereas pulmonary artery perfusion remained unchanged. Ablation of the bronchial artery after the initiation of tumor growth resulted in a decrease in tumor volume over a subsequent course of 4 weeks. These results demonstrate that although the existing pulmonary circulation can supply the metabolic needs for tumor initiation, further growth of the tumor requires angiogenesis from the highly proliferative bronchial circulation. This model may be useful to investigate new therapeutic approaches that target specifically the bronchial circulation.
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U2 - 10.1158/0008-5472.CAN-16-1131
DO - 10.1158/0008-5472.CAN-16-1131
M3 - Article
C2 - 27569207
AN - SCOPUS:84991573152
VL - 76
SP - 5962
EP - 5969
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 20
ER -