Rapid growth of human cancer cells in a mouse model with fibrin clot subrenal capsule assay.
Rapid in vivo growth of cultured human cancer or leukemia cells was achieved by implantation into the subrenal capsule of mice. A solid structure, necessary for accurate implantation and measurement of tumor growth in this model, was provided by stepwise addition of fibrinogen and thrombin to the tumor cells, leading to rapid enzymatic formation of a solid tumor-fibrin matrix. Human leukemia and epithelial cancers increased in volume between 6- and 40-fold when measured 6-10 days after implantation into normal or immunosuppressed mice. Immunosuppression of host CD-1 mice was achieved by cyclosporine given daily after tumor implantation, cyclophosphamide given preimplantation combined with cyclosporine, or whole-body irradiation given preimplantation. Confirming the validity of tumor measurements, tumor histology in the immunosuppressed mice revealed cell proliferation, invasion, and neovascularization. Similarly, no artifactual measurement of tumor growth was observed by nonviable cancer cells, implanted after in vitro exposure to a known cytotoxic concentration of thiotepa. This model provides an economical, short-term technique for the in vivo study of human tumor growth, for the evaluation of new cancer therapies, and for in vitro - in vivo drug activity correlations in specific types of human cancer or leukemia cell lines.
Fingert
H J
HJ
Chen
Z
Z
Mizrahi
N
N
Gajewski
W H
WH
Bamberg
M P
MP
Kradin
R L
RL
D000818:Animals; D003110:Colonic Neoplasms / Q000473:pathology*; D005260:Female; D005337:Fibrin / Q000032:analysis*; D006801:Humans; D007165:Immunosuppression Therapy; D007621:Karyotyping; D007668:Kidney; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008545:Melanoma / Q000473:pathology*; D008722:Methods; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous; D001749:Urinary Bladder Neoplasms / Q000473:pathology*; D014846:Vulvar Neoplasms / Q000473:pathology*
D005337:Fibrin