Decreased DNA ploidy may constitute a mechanism of the reduced malignant behavior of B16 melanoma in aged mice.
Numerous data demonstrate a lower aggressiveness of tumors in aged as compared to young patients. The mechanisms underlying this phenomenon have not yet been completely elucidated. Several mechanisms have been shown, such as reduced tumor cell proliferation, increased apoptosis, immune response modifications and reduced angiogenesis in aged organism tumors. In the present study we report an incidentally found, not yet described mechanism, of the age-related reduced tumor progression, namely a decreased ploidy in B16 melanoma growing in old (near diploidy) as compared to young mice (tetraploidy). We surprisingly observed that tumor cells from aged mice were of smaller cell and nuclear size than those of young animals. Flow cytometry forward scatter data also showed a smaller cell size of melanoma cells from old mice. DNA flow cytometry profile comparison demonstrated that while B16 melanoma cells from young animals contained a high percentage of tetraploid cells, those derived from old animals were mostly close to diploid. A high importance has recently been attributed to aneuploidy as being at the origin of the genetic instability of neoplasia. Our results may support this notion. The transit from tetraploidy to near euploidy in melanoma cells growing in aged mice might avoid the genetic instability inherent to tumor progression.
Itzhaki
Orit
O
Department of Pathology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Skutelsky
Ehud
E
Kaptzan
Tatiana
T
Siegal
Annette
A
Sinai
Judith
J
Schiby
Ginnette
G
Michowitz
Moshe
M
Huszar
Monica
M
Leibovici
Judith
J
D000375:Aging / Q000235:genetics* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D048429:Cell Size; D004273:DNA, Neoplasm / Q000032:analysis*; D018450:Disease Progression; D008546:Melanoma, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011003:Ploidies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D004273:DNA, Neoplasm; D019253:Proto-Oncogene Proteins c-bcl-2