A bone metastasis model with osteolytic and osteoblastic properties of human lung cancer ACC-LC-319/bone2 in natural killer cell-depleted severe combined immunodeficient mice.
Lung cancer is commonly associated with multiple-organ metastasis, and bone is a frequent metastatic site for lung cancer. Lung cancer frequently develops osteolytic, and less frequently osteoblastic, metastasis to bone. Osteolytic metastasis models of lung cancer have been reported, but no osteoblastic metastasis model is available for lung cancer. In the present study, we established a reproducible model of human lung cancer with both osteolytic and osteoblastic changes in natural killer cell-depleted severe combined immunodeficient mice. Intravenous inoculation of ACC-LC-319/bone2 cells resulted in the development of metastatic colonies in the lung, liver, and bone of the mice. As assessed sequentially by X-ray photographs, osteolytic bone lesions were observed by day 28, and then osteoblastic lesions were detected by day 35. Histological examination revealed the presence of bony spurs, a hallmark of osteoblastic bone metastasis, where osteoclasts were hardly observed. Treatment with an anti-human vascular endothelial growth factor antibody, bevacizumab, as well as zoledronate, inhibited the number of experimental bone metastases, including osteoblastic changes produced by ACC-LC-319/bone2 cells. These results indicate that our bone metastasis model by ACC-LC319/bone2 might be useful to understand the molecular pathogenesis of osteolytic and osteoblastic metastasis, and to identify molecular targets to control bone metastasis of lung cancer.
Otsuka
Shinsaku
S
Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, University of Tokushima Gradate School, Tokushima, 770-8503, Japan.
Hanibuchi
Masaki
M
Ikuta
Kenji
K
Yano
Seiji
S
Goto
Hisatsugu
H
Ogino
Hirokazu
H
Yamada
Tadaaki
T
Kakiuchi
Soji
S
Nishioka
Yasuhiko
Y
Takahashi
Takashi
T
Sone
Saburo
S
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001859:Bone Neoplasms / Q000556:secondary*; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000627:therapeutic use; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000032:analysis / Q000502:physiology; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D010006:Osteoblasts / Q000473:pathology; D010014:Osteolysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D000077211:Zoledronic Acid
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004164:Diphosphonates; D019332:Endothelin-1; D007093:Imidazoles; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000077211:Zoledronic Acid