BK virus-induced osteosarcoma (Os515) as a model of human osteosarcoma.
BK virus was isolated by Gardner et al in 1971 from the urine of an immunosuppressed patient with a kidney allograft. Antibodies to this virus are ubiquitous in the general populations worldwide, but the oncogenic capacity of BKV in humans had not been reported. The virus transformed in vitro permissive human and non-permissive animal cells, and the transformed cells had the T antigen. Intracerebral and intravenous inoculation of BKV in newborn hamsters induced malignant tumours (mainly ependymomas, malignant insulinomas, and osteosarcomas). Subcutaneous and intraperitoneal routes were also effective. The virus was only rescued from a few tumours by fusion with human embryonic cells or Vero cells. Brain tumours appeared earlier and osteosarcomas developed in animals which survived for more than 6 months. Many of the osteosarcomas were bony and grew slowly with frequent lung metastases, and a few osteosarcomas were soft and grew rapidly without lung metastases. Experimental targeting chemotherapy with doxorubicin (DX)-containing immunoliposomes was performed against Os515 osteosarcoma. In in vitro experiments, DX-Lip-MoAb29 showed a more significant inhibitory effect on cultured Os515 cells than free Dx and DX-Lip. DX-Lip DNP had less effect. In in vivo experiments, DX-Lip-MoAb29 suppressed the growth of Os515 tumour isografts in hamsters and prolonged the survival of recipients more significantly than free DX.
Sekiguchi
M
M
Department of Surgery I, Saitama Medical School, Japan.
Miyazaki
S
S
Fujikawa
K
K
Shiroko
Y
Y
Asanuma
K
K
D000818:Animals; D000831:Animals, Newborn; D001739:BK Virus; D001932:Brain Neoplasms / Q000473:pathology* / Q000821:virology; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004317:Doxorubicin / Q000627:therapeutic use; D004622:Embryo, Mammalian; D004806:Ependymoma / Q000473:pathology / Q000821:virology; D006801:Humans; D007340:Insulinoma / Q000473:pathology / Q000821:virology; D008561:Membrane Fusion; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000821:virology; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D014709:Vero Cells
D004317:Doxorubicin