Analysis of tumor vascularization in a mouse model of metastatic lung cancer

• Published in: Scientific reports Vol. 9; no. 1; pp. 16029 - 10
• Main Authors: Sukhbaatar, Ariunbuyan, Sakamoto, Maya, Mori, Shiro, Kodama, Tetsuya
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05-11-2019; Nature Publishing Group
• Subjects: 59; 59/5; 631/1647/767/70; 64/60; 692/4028/67/322; Animals; Arterioles; Bioluminescence; Blood Vessels - diagnostic imaging; Blood Vessels - physiology; Cell activation; Chemotherapy; Computed tomography; Disease Models, Animal; Drug delivery; Female; Histology; Humanities and Social Sciences; Indocyanine Green - chemistry; Liposomes; Liposomes - chemistry; Lung - blood supply; Lung - pathology; Lung cancer; Lung Neoplasms - blood supply; Lung Neoplasms - pathology; Lymph nodes; Lymph Nodes - pathology; Male; Metastases; Metastasis; Mice; multidisciplinary; Neoplasm Metastasis; Neovascularization, Pathologic; Permeability; Science; Science (multidisciplinary); Tumor cells; Tumors; Vascularization; X-Ray Microtomography
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-52144-2

Therapies targeting tumor vasculature would improve the treatment of lung metastasis, although the early changes in vascular structure are incompletely understood. Here, we show that obstructive metastatic foci in lung arterioles decrease the pulmonary vascular network. To generate a mouse model of lung metastasis activation, luciferase-expressing tumor cells were inoculated into the subiliac lymph node (SiLN) of an MXH10/Mo-
lpr
/
lpr
mouse, and metastatic tumor cells in the lungs were activated by SiLN resection. Activation of metastases was monitored by
in vivo
bioluminescence imaging. Pulmonary blood vessel characteristics were analyzed using
ex vivo
micro-computed tomography. The enhanced permeability and retention (EPR) effect in neovasculature after tumor cell activation was evaluated from the accumulation of intravenously injected indocyanine green (ICG) liposomes. Metastatic foci in lung arterioles were investigated histologically. Micro-computed tomography revealed decreases in pulmonary blood vessel length, volume and number of branching nodes during the early stage of metastasis caused by metastatic foci. ICG liposome accumulation by the EPR effect was not detected. Histology identified metastatic foci in lung arterioles. The lack of an EPR effect after the formation of metastatic foci in lung arterioles makes conventional systemic chemotherapy ineffective for lung metastasis. Thus, alternative therapeutic methods of drug delivery are needed.