Establishment and characterization of a new highly metastatic human osteosarcoma cell line.
Osteosarcoma is the most common primary malignancy of bone in children and young adults. There is a paucity of tumorigenic and highly metastatic human osteosarcoma cell lines that have not been further transformed by exogenous means. Here we establish and characterize a highly metastatic human osteosarcoma cell line that is derived from a poorly metastatic MG63 line through serial passage in nude mice via intratibial injections. The occasional pulmonary metastases developed from MG63 were harvested and repassaged in mice until a highly metastatic subline (MG63.2) was established. The parental MG63 and highly metastatic MG63.2 cells were further characterized in vitro and in vivo. MG63.2 cells demonstrated increased cell migration and invasion compared to the parental MG63 cells. Conversely, cell adhesion was significantly greater in MG63 cells when compared to the MG63.2 cells. MG63.2 cells grew at a slightly slower rate than that of the parental cells. When injected into nude mice, MG63.2 cells had a greater than 200-fold increase in developing pulmonary metastases compared to the parental MG63 cells. MG63.2 cells also formed larger primary tumors when compared to the parental MG63 cells. Further analysis revealed that ezrin expression was up-regulated in the metastatic MG63.2 cells. Interestingly, expressions of MMP-2 and MMP-9 were down-regulated, and expression of TIMP-2 was up-regulated in the MG63.2 cells. Taken together, we have established and characterized a highly metastatic human osteosarcoma cell line that should serve as a valuable tool for future investigations on the pathogenesis, metastasis, and potential treatments of human osteosarcoma.
The Children's Hospital and Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education of China, Chongqing Medical University, 400016, Chongqing, China.
Yuxi
Y
Su
Xiaoji
X
Luo
Bai-Cheng
BC
He
Yi
Y
Wang
Liang
L
Chen
Guo-Wei
GW
Zuo
Bo
B
Liu
Yang
Y
Bi
Jiayi
J
Huang
Gao-Hui
GH
Zhu
Yun
Y
He
Quan
Q
Kang
Jinyong
J
Luo
Jikun
J
Shen
Jin
J
Chen
Xianqing
X
Jin
Rex C
RC
Haydon
Tong-Chuan
TC
He
Hue H
HH
Luu
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D018215:Osteoblastoma / Q000235:genetics / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers