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Random Process of Metastasis and Generation of Heterogeneity in a Mouse Sarcoma Line

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Specialty Oncology
Date 1993 Jan 1
PMID 8449827
Citations 1
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Abstract

The process of metastasis was analyzed in 505-05-01 cells, an established line of a methyl-cholanthrene-induced mouse sarcoma, by tagging the cells with the pSV2neo plasmid. A dominant clone was identified which, upon transplantation together with other clones, overgrew tumors in the kidney capsule. However, when this clone was transplanted in a mouse collaterally with recessive clones, both clones grew at the same rate and metastasized to the lung at an equal frequency. This suggests that the process of metastasis in this particular sarcoma line is stochastic, the dominant population having a better chance to colonize to the lung. The dominant neomycin-resistant clone was transfected with another marker plasmid, pY3, which confers resistance to hygromycin. Results of mixed inoculation of 9 independently isolated clones revealed the hierarchy of dominance among clones. This indicated the existence of heterogeneity within the parental clone. Upon mixed inoculation with hygromycin-resistant clones, the parental clone overgrew in the tumors. This indicated that some clone had changed its phenotype to become less aggressive. Thus, the direction of phenotypic drift in vitro seems to be random in terms of behavior in vivo.

Citing Articles

p53 gene mutation and loss of heterozygosity of chromosome 11 in methylcholanthrene-induced mouse sarcomas.

Shimokado K, Watanabe H, Sumii M, Miyagawa K, Kamiya K, Dohi K Jpn J Cancer Res. 1998; 89(3):269-77.

PMID: 9600120 PMC: 5921802. DOI: 10.1111/j.1349-7006.1998.tb00558.x.

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