The effects of aging on tumor growth and angiogenesis are tumor-cell dependent

May J. Reed, Nathan Karres, Daniel Eyman, Abigail Cruz, Rolf A. Brekken, Stephen Plymate

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

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/B16 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.

Original languageEnglish (US)
Pages (from-to)753-760
Number of pages8
JournalInternational Journal of Cancer
Volume120
Issue number4
DOIs
StatePublished - Feb 15 2007

Keywords

  • Aged
  • Blood vessels
  • Matrix metalloproteinases
  • Mice
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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