Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

Genotypic and Phenotypic Evolution of a Murine Tumor During Its Progression In Vivo Toward Metastasis

Genotypic and Phenotypic Evolution of a Murine Tumor During Its Progression In Vivo Toward... Abstract To follow the cellular progeny of the multiple-drug-marked benign murine tumor cell line MDW4 during its progression in vivo toward metastatic spread in DBA/2 mice, the following parameters were analyzed: retention of the drug-resistant markers ouabain resistance (OuaR) and thioguanine resistance (ThgR), lectin-resistance pattern (WGAR), and the karyotype of cell populations (and clones derived from these cells) removed at intervals from the solid tumor growing at the site of inoculation, as well as distant metastatic nodules. It was determined that the initially homogeneous inoculum composed of OuaR, ThgR, and WGAR hypotetraploid cells (mode: 68±2 chromosomes) was gradually overgrown and replaced by a new population of cells that were either OuaR or ouabain-sensitive but that became thioguanine-and lectin-sensitive and hyperploid (mode: 95±5). Regardless of the composition of the individual drug marker combinations, only cells with high chromosome contents were found to be able to disseminate to distant visceral organs and to rapidly produce metastases upon sc or iv reinjection. The presence of the same number of metacentric chromosomes in metastatic cells as in MDW4 and the coextinction of two recessive drug-resistant markers (WGAR and ThgR) suggested that cells endowed with invasive-metastatic potential represent the product of spontaneous somatic hybridization between the original nonmetastatic MDW4 cells and normal host cells of unknown origin. Such a fusion was followed by more or less extensive chromosome segregation that accounts for the karyotype mosaicism and the occasional drug marker heterogeneity identified in cell populations of metastatic nodules. 2 Supported by research grants from the National Cancer Institute of Canada. 3 Animals were maintained under the guidelines set forth by the Animal Care Committee, Queen's University. This content is only available as a PDF. Author notes 4 Cancer Research Division, Department of Pathology, Queen's University, Kingston, Ontario, Canada K7L 3N6. 5 Research associate of the National Cancer Institute of Canada. 6 We thank Ms. Shan Man and Mrs. Majka Florian for their expert technical assistance and Mrs. Beverley Fluhrer and Mrs. Beverley Muller for excellent secretarial assistance. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JNCI: Journal of the National Cancer Institute Oxford University Press

Genotypic and Phenotypic Evolution of a Murine Tumor During Its Progression In Vivo Toward Metastasis

Download PDF
9 pages

Loading next page...
 
/lp/oxford-university-press/genotypic-and-phenotypic-evolution-of-a-murine-tumor-during-its-bSSBpXh0io

References (0)

References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.

Publisher
Oxford University Press
ISSN
0027-8874
eISSN
1460-2105
DOI
10.1093/jnci/71.1.183
Publisher site
See Article on Publisher Site

Abstract

Abstract To follow the cellular progeny of the multiple-drug-marked benign murine tumor cell line MDW4 during its progression in vivo toward metastatic spread in DBA/2 mice, the following parameters were analyzed: retention of the drug-resistant markers ouabain resistance (OuaR) and thioguanine resistance (ThgR), lectin-resistance pattern (WGAR), and the karyotype of cell populations (and clones derived from these cells) removed at intervals from the solid tumor growing at the site of inoculation, as well as distant metastatic nodules. It was determined that the initially homogeneous inoculum composed of OuaR, ThgR, and WGAR hypotetraploid cells (mode: 68±2 chromosomes) was gradually overgrown and replaced by a new population of cells that were either OuaR or ouabain-sensitive but that became thioguanine-and lectin-sensitive and hyperploid (mode: 95±5). Regardless of the composition of the individual drug marker combinations, only cells with high chromosome contents were found to be able to disseminate to distant visceral organs and to rapidly produce metastases upon sc or iv reinjection. The presence of the same number of metacentric chromosomes in metastatic cells as in MDW4 and the coextinction of two recessive drug-resistant markers (WGAR and ThgR) suggested that cells endowed with invasive-metastatic potential represent the product of spontaneous somatic hybridization between the original nonmetastatic MDW4 cells and normal host cells of unknown origin. Such a fusion was followed by more or less extensive chromosome segregation that accounts for the karyotype mosaicism and the occasional drug marker heterogeneity identified in cell populations of metastatic nodules. 2 Supported by research grants from the National Cancer Institute of Canada. 3 Animals were maintained under the guidelines set forth by the Animal Care Committee, Queen's University. This content is only available as a PDF. Author notes 4 Cancer Research Division, Department of Pathology, Queen's University, Kingston, Ontario, Canada K7L 3N6. 5 Research associate of the National Cancer Institute of Canada. 6 We thank Ms. Shan Man and Mrs. Majka Florian for their expert technical assistance and Mrs. Beverley Fluhrer and Mrs. Beverley Muller for excellent secretarial assistance.

Journal

JNCI: Journal of the National Cancer Institute – Oxford University Press

Published: Jul 1, 1983

There are no references for this article.