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American Journal of Pathology, Vol 101, 345-352, Copyright © 1980 by American Society for Investigative Pathology

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In vitro and in vivo adherence of tumor cell variants correlated with tumor formation

J Varani, EJ Lovett, S Elgebaly, J Lundy and PA Ward

Murine fibrosarcoma variants that differed greatly in tumorgenicity, in vivo growth rate, and rate of spontaneous metastasis formation were compared for their ability to induce tumors in the lungs of syngeneic mice after intravenous injection of a suspension of single cells. Significantly more tumors were observed in the lungs of mice that received 1 x 10(5) of the cells of high malignant potential than in the lungs of animals that received 1 x 10(5) cells of lower malignant potential (54 tumors per animal vs 3 tumors per animal). When the tumor cells were prelabeled in culture for 24 hours with 125I-IUDR prior to intravenous injection, it was found that both the "high" and "low malignant" cells rapidly accumulated in the lungs (55-59% of the radioactivity was found in the lung tissue by 5 minutes after injection). However, by 4 hours only 4% of the low malignant cells (as indicated by the amount of radioactivity present) were still in the lungs, while a significantly higher percentage (13%) of the high malignant cells were still present in the lungs. The difference between the high and low malignant cells with regard to ability to remain sequestered in the lungs of syngeneic mice and to subsequently form tumors in the lungs of these animals correlated with the ability of the cells to form stable attachments to monolayers of endothelial cells in culture. While both the high and low malignant cells attached at the same rate to monolayers of bovine endothelial cells, once the cells were attached, the low malignant cells were released by trypsin treatment more easily than the high malignant cells. These observations suggest that the difference in malignant potential between the variants may be due, at least in part, to differences in ability to form stable attachments.

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