Evidence for single-cell origin of 3-methylcholanthrene-induced fibrosarcomas in mice with cellular mosaicism

Area of Science:

• Oncology
• Genetics
• Biochemistry

Background:

• Fibrosarcomas are malignant tumors originating from connective tissue.
• X-chromosome inactivation is a process where one of the two X chromosomes is randomly inactivated in female mammals.
• Mosaicism refers to the presence of two or more populations of cells with different genotypes in one individual.

Purpose of the Study:

• To determine the cellular origin of fibrosarcomas induced by 3-methylcholanthrene in mice with X-chromosome inactivation mosaicism for the phosphoglycerate kinase (PGK-1) gene.

Main Methods:

• Induction of fibrosarcomas via subcutaneous injection of 3-methylcholanthrene in Pgk-1a/Pgk-1b mice.
• Analysis of phosphoglycerate kinase (PGK-1) expression in tumor cells using electrophoretic mobility.

Main Results:

• Seven out of eight (88%) fibrosarcoma cases exhibited only one type of phosphoglycerate kinase (PGK-1).
• This finding was determined by analyzing the electrophoretic mobility of PGK-1 in tumor cells.
• The presence of a single PGK-1 type suggests a clonal origin of the tumors.

Conclusions:

• Fibrosarcomas induced by 3-methylcholanthrene in this mouse model arise from a single progenitor cell.
• This study provides evidence for the single-cell origin of chemically induced tumors in mosaic mice.