Decorin suppresses lung metastases of murine osteosarcoma.
Lung metastasis is the most crucial event affecting the therapeutic outcome of osteosarcoma. The prevention of lung metastasis is therefore important in improving the prognosis of patients with osteosarcoma. Decorin is a major extracellular matrix protein which has become the focus of various cancer studies. The biological role of decorin in osteosarcoma has yet to be clarified. The aim of this study was to examine the potential of decorin as a novel biological target for the treatment of osteosarcoma. In this study, the LM8 murine osteosarcoma cell line (LM8) with high metastatic potential to the lung was used. The two cell lines established were LM8-DCN which stably expressed human decorin (hDCN) and LM8-mock, established as a control. The LM8-DCN cell line was subcutaneously injected into the backs of mice. Significantly fewer pulmonary metastases were observed in mice with LM8-DCN compared to mice inoculated with LM8 and LM8-mock (P<0.001). In addition, the mice in the LM8-DCN inoculated group survived significantly longer than those in the LM8 and LM8-mock inoculated group, based on the Kaplan-Meier survival analysis and log-rank tests (P<0.005). The effect of decorin on the growth rates, motility and invasion ability of LM8 was investigated in vitro. There was no difference in the morphology and growth rates, but the motility and invasion of LM8 were inhibited by decorin. These results suggest that decorin has the therapeutic potential to prevent lung metastasis in osteosarcoma.
Shintani
Ken
K
Department of Orthopaedic Surgery, Mie University Faculty of Medicine, Mie, Japan.
Matsumine
Akihiko
A
Kusuzaki
Katsuyuki
K
Morikawa
Joji
J
Matsubara
Takao
T
Wakabayashi
Toru
T
Araki
Kentaro
K
Satonaka
Haruhiko
H
Wakabayashi
Hiroki
H
Iino
Takahiro
T
Uchida
Atsumasa
A
D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000473:pathology / Q000517:prevention & control*; D002465:Cell Movement; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000517:prevention & control* / Q000556:secondary; D011509:Proteoglycans / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured
C546878:DCN protein, human; C546879:Dcn protein, mouse; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta