| Abstract |
Hematogenous metastasis to the lungs is a major complication in patients
with different types of sarcomas. Investigations of the mechanisms of
tumor spread and the search for new treatment modalities have been
hindered by the lack of appropriate in vivo model systems. We have now
established such a model involving the experimental metastasis of human
osteosarcoma (HOS) cells in immunodeficient nude mice. Malignant subdones
were isolated from HOS cells transformed by either the viral Ki-ras or a
mutated cellular Ha-ras oncogene. The ras transformants, unlike most other
human malignancies, were capable of forming pulmonary metastases following
intravenous transplantation into mice, an assay that mimics the later
events of blood-borne metastasis. One of the v-Ki-ras-transformed cell
lines, designated KRIB, formed lung tumors in 80%-100% of recipient mice
with a median number of 20 nodules per animal. The tumors, composed of
poorly differentiated human sarcoma cells, were easily detected as
macroscopic nodules within 5 weeks post inoculation. Detection and
isolation of metastatic cells from cultured lung tissue was improved by
the use of selectable geneticin-resistant KRIB cells, obtained by
transfection with pSV2neo DNA. The ability to test the metastatic
potential of human KRIB sarcoma cells in mice makes this model valuable
for both basic and applied research on factors affecting tumor
dissemination to the lungs.
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