Establishment and characterization of a murine osteosarcoma cell line (LM8) with high metastatic potential to the lung.
We established a murine osteosarcoma cell line (LM8) with high metastatic potential to the lung from murine Dunn osteosarcoma using 8 repeated Fidler's procedures. We performed the biological characterization of the LM8 and the maternal Dunn cell lines in vitro and in vivo. Morphologically, LM8 possesses many fillopodial protrusions, lamellipodial structures surrounding the cell surface and membrane ruffles suggesting enhanced cell motility. The increased matrix metalloproteinase (MMP) 2 activity of this cell line might help cell invasion after penetration of the endothelial (mesothelial) cell layer. This cell line exhibited high in vitro invasive activity when seeded onto the mesothelial cell monolayer. Higher expression of VEGF mRNA in this cell line might facilitate neovascularization at the site of metastasis, resulting in extremely high metastatic potency after i.v. injection. LM8 also showed a high metastatic incidence (7/7) to the lung even after s.c. transplantation into the back space of mice. This cell line can provide an excellent tool for studying inhibitory agents against pulmonary metastasis as well as the various important factors involved in metastasis of osteosarcoma.
Asai
T
T
Department of Orthopaedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
Ueda
T
T
Itoh
K
K
Yoshioka
K
K
Aoki
Y
Y
Mori
S
S
Yoshikawa
H
H
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism / Q000556:secondary*; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D009363:Neoplasm Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000469:Alkaline Phosphatase; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2