Macrophage-recognized molecules of apoptotic cells are expressed at higher levels in AKR lymphoma of aged as compared to young mice.
While a direct relation between aging and tumorigenesis is well established, a slower tumor progression rate was reported in old as compared to young cancer patients. The mechanisms responsible for the less aggressive behavior of tumors in the aged, are largely unknown. We have recently shown an increase in apoptotic cell death in tumors derived from aged as compared to young animals in the AKR lymphoma. This was shown by DNA flow cytometry and by the ladder type DNA fragmentation in agarose gel electrophoresis. Analysis of the expression of genes involved in apoptosis in tumors derived from young and old animals showed a lower bcl-2 expression in those from the aged. The Fas antigen, on the contrary, displayed higher expression levels on lymphoma cells derived from old than on those from young mice. Apoptotic cells are recognized and phagocytosed mainly by macrophages. One molecular property of apoptotic cells which is recognized by macrophages is a loss in cell surface sialic acid concomitantly uncovering galactose residues. While comparing the "eat me status" phenotype of the tumor cells derived from young and aged animals, by the use of lectins recognizing sialic acid and galactose residues, FACS analysis showed a decrease in cell surface sialic acid and a gain in galactose residues in aged as compared to young mice. Moreover, Western blot analysis showed that a 130 Kda sialylated membrane glycoprotein was expressed at a lower level in tumors from the old as compared to young mice. Our results, at both the cellular and molecular levels, particularly with regard to molecules recognized by macrophages, indicate that increased apoptotic cell death in tumors from old as compared to those from young animals constitutes, as we have previously suggested, one of the mechanisms of the age-related decrease in tumor progression rate.
Itzhaki
O
O
Department of Pathology, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Skutelsky
E
E
Kaptzan
T
T
Siegal
A
A
Michowitz
M
M
Sinai
J
J
Huszar
M
M
Nafar
S
S
Leibovici
J
J
D000375:Aging; D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D053938:DNA Fragmentation; D005434:Flow Cytometry; D008223:Lymphoma / Q000276:immunology* / Q000473:pathology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008806:Mice, Inbred AKR; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis
D019253:Proto-Oncogene Proteins c-bcl-2