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 HRCT scans (276% increase in large tumors), parallels the growth in tumor volume, while 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 while 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.

CT Perfusion in Patients with Lung Cancer: Squamous Cell Carcinoma and Adenocarcinoma Show a Different Blood Flow

“…The first comment concerns ID10, the AC lesion characterized by the lowest perfusion and shown in Figure 5 . This lesion is a very small peripheral carcinoma, one of the smallest examined, located in the subpleural parenchyma, probably characterized by a predominant pulmonary circulation, which could not have activated the angiogenesis process yet [ 37 ]. As regards the other two AC lesions with a low perfusion, ID5 in Figure 6(a) and ID15 in Figure 6(b) , these share similar properties that could explain their low perfusion.…”

Angiogenesis in the lung

“…Furthermore, ablation of the bronchial artery after the initiation of tumour growth resulted in significant reduction in tumour volumes at 4 weeks post‐ablation (Eldridge et al . ).…”

“…In the few reported studies, differences exist between pulmonary and bronchial endothelial cells (Moldobaeva & Wagner, ; Eldridge et al . ), as well as aortic endothelial cells (Moldobaeva et al . ) with regard to in vitro proliferative capacity and surface marker expression.…”

“…; Eldridge et al . 2016 ). Yet analysis can be complicated by vasodilation and increased blood flow, which are not equivalent to neovascularization.…”

The roles of tumor-derived exosomes in non-small cell lung cancer and their clinical implications

“…It has been shown that cancer-associated fibroblasts (CAFs) in the tumor microenvironment can secrete exosomes containing lipids, amino acids, and TCA-cycle intermediates which can promote tumor growth under nutrient-stressed or nutrient-deprivation conditions [ 32 ]. Angiogenesis is also vital for tumor growth since tumor vessels are the important sources of nutrient substances in the tumor cells [ 33 ]. Tumor-derived exosomes can accelerate angiogenesis and tumor growth in a TGFβ1 (transforming growth factor β1)-dependent pathway to stimulate fibroblasts to differentiate into tumor-promoting stromal myofibroblasts [ 34 ].…”