title: Bronchial Artery Angiogenesis Drives Lung Tumor Growth.
abstract: 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. Cancer Res; 76(20); 5962-9. ©2016 AACR.
authors: Departments of Medicine and Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland.
authors: Lindsey
authors: L
authors: Eldridge
authors: Departments of Medicine and Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland.
authors: Aigul
authors: A
authors: Moldobaeva
authors: Departments of Medicine and Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland.
authors: Qiong
authors: Q
authors: Zhong
authors: Departments of Medicine and Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland.
authors: John
authors: J
authors: Jenkins
authors: Departments of Medicine and Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland.
authors: Michael
authors: M
authors: Snyder
authors: Departments of Medicine and Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland.
authors: Robert H
authors: RH
authors: Brown
authors: Departments of Medicine and Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland.
authors: Wayne
authors: W
authors: Mitzner
authors: Departments of Medicine and Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland. wagnerem@jhmi.edu.
authors: Elizabeth M
authors: EM
authors: Wagner
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D001981:Bronchial Arteries / Q000502:physiology*; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000473:pathology*; D018919:Neovascularization, Physiologic; D011651:Pulmonary Artery / Q000502:physiology; D011652:Pulmonary Circulation; D051381:Rats; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden