The effects of aging on tumor growth and angiogenesis are tumor-cell dependent.
It is generally accepted that histologically similar tumors grow more slowly, with less angiogenesis, in aged mice relative to young mice. We subcutaneously implanted TRAMP-C2 tumor cells, a prostate cancer cell line not previously examined in aging, into syngeneic C57/Bl6 young (4 month) and aged (20 month) mice and compared tumor growth and angiogenesis. Unexpectedly, the prostate tumors grew as fast in aged as in young mice. Angiogenesis in TRAMP-C2 tumors was robust, with no differences between the young and aged mice in the number of vessels, distribution of vessel sizes or features of vessel maturation. Aged mice had lower levels of serum testosterone than the young mice. VEGF levels were similar in the tumors and sera of the young and aged mice. Comparison with B16/F10 melanoma, a cancer cell line that is representative of previous studies in aged mice, showed that B16/F10 tumors grew minimally in the aged mice. In contrast to the B16/F10, TRAMP-C2 tumors had an extracellular matrix with significantly higher levels of MMP2 and MMP9 expression and activity. These unique results demonstrate that tumor progression can be as robust in aged tissues as young tissues. The ability of aged mice to grow large, vascularized prostate tumors is associated with high levels of MMP2/9 activity that may produce a permissive environment for tumor growth and angiogenesis. These data demonstrate that tumor-cell specific features determine the effect of aging on tumor growth and angiogenesis.
Reed
May J
MJ
Department of Medicine, University of Washington, Harborview Medical Center, Seattle, WA 98104, USA. mjr@u.washington.edu
Karres
Nathan
N
Eyman
Daniel
D
Cruz
Abigail
A
Brekken
Rolf A
RA
Plymate
Stephen
S
D000375:Aging / Q000502:physiology*; D000727:Androgen-Binding Protein / Q000235:genetics; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D001808:Blood Vessels / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000097:blood; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000727:Androgen-Binding Protein; D000952:Antigens, Polyomavirus Transforming; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D042461:Vascular Endothelial Growth Factor A; C027519:probasin; C467480:vascular endothelial growth factor A, mouse; D013739:Testosterone; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9