Anti-tumor necrosis factor therapy inhibits lung metastasis in an osteosarcoma cell line.
BACKGROUND
Osteosarcoma is the most common primary malignancy of bone, and patients often develop pulmonary metastases. In a previous study, tumor necrosis factor (TNF)-α treatment of human osteosarcoma cells increases their metastatic ability in an animal model. TNF-α can act as a tumor necrosis factor and also as a tumor-promoting factor. In the present study, the effect of a TNF-α inhibitor on osteosarcoma aggressiveness and pulmonary metastases was investigated in vitro and in vivo.


METHODS
The effect of infliximab, a TNF-α inhibitor, on a metastatic osteosarcoma 143B cell growth and motility was investigated in vitro. An orthotopic xenograft model of 143B cell growth and spontaneous metastasis in SCID mice was used to assess the in vivo effect of infliximab.


RESULTS
Infliximab greatly reduced cell motility and pulmonary metastases in 143B cells. The mechanism of pulmonary metastasis inhibition involved decreased expression of CXC chemokine receptor 4 (CXCR4), Rho (small GTPase protein), and its effector.


CONCLUSIONS
These results suggest a novel role for TNF-α inhibition in the reduction or prevention of pulmonary metastases of osteosarcoma in this animal model. TNF-α inhibition may become a preventive therapeutic option for the pulmonary metastases of osteosarcoma.
Department of Orthopedic Surgery, Mie University Graduate School of Medicine, Tsu, Japan.
Hiroaki
H
Kato
Hiroki
H
Wakabayashi
Yohei
Y
Naito
Sho
S
Kato
Taro
T
Nakagawa
Akihiko
A
Matsumine
Akihiro
A
Sudo
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004334:Drug Administration Schedule; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000069285:Infliximab; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab