A progression series of murine fibrosarcoma separates proliferative and invasive transformation characteristics

Background: Sarcomas are a heterogeneous group of mesenchymal tumours, with a great variability in their clinical behaviour. While our knowledge of sarcoma initiation advanced rapidly in recent years, relatively little is known about mechanisms of sarcoma progression. We report the establishment and characterization of a murine fibrosarcoma progression series consisting of four sarcoma cell lines, JUN-1, JUN-2, JUN-2fos-3, and JUN-3.

Material and Methods: JUN-1 and -2 were established from a single tumour initiated in a H2K/v-jun transgenic mouse, JUN-3 originates from a different tumour in the same animal, and JUN-2fos-3 results from a targeted in vitro transformation of the JUN-2 cell line. In each cell line of the series, transformation and metabolic characteristics have been assessed together with the expression of jun and fos oncoproteins.

Results: The JUN-1, -2, and -3 cell lines represent a linear progression from the least transformed JUN-2 to the most transformed JUN-3, with regard both to cell proliferation, motility and invasiveness. In contrast, the JUN-2fos-3 cell line exhibits a unique transformation pattern, with little deregulation of cell growth and proliferation, but pronounced motility and invasiveness. Interestingly, it is especially the migratory ability and not that much the other transformation traits that determines the prevailing metabolic phenotype of the cells. For the highly motile cell lines JUN-2fos-3 and JUN-3, their dependency on oxidative phosphorylation is increased and, importantly, their respiration is significantly more effective than the respiratory chain of JUN-1 and JUN-2 cells. On the contrary, physiological respiration of the noninvasive and poorly transformed JUN-2 cells is very similar to the theoretical maximum utilization of oxygen and shows a very small capacity reserve. Besides being highly transformed, the JUN-3 cell line exhibits the highest anchorage-independent growth and sarcosphere forming capacity, and could provide a convenient source of sarcoma stem cells.

Conclusions: We believe that this progression series could be very valuable for deciphering crucial aspects of sarcoma progression.

No conflict of interest.