Contrasting effects of IGF binding protein-3 expression in mammary tumor cells and the tumor microenvironment

Tiffany Scully, Carolyn D. Scott, Sue M. Firth, John E. Pintar, Stephen M. Twigg, Robert C. Baxter

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


IGFBP-3 has both stimulatory and inhibitory effects on cancer progression. The growth of EO771 mammary carcinoma cells as syngeneic tumors in C57BL/6 mice is reduced in Igfbp3-null (BP3KO) mice, suggesting that systemic IGFBP-3 enhances tumor progression. In this study we assessed the growth of EO771 cells expressing human IGFBP-3 in BP3KO mice. Cells expressing hIGFBP-3 showed decreased proliferation in vitro and increased levels of IGF-1 receptor (IGF1R) protein but not mRNA, consistent with sequestration of endogenous IGF by IGFBP-3. The growth rate of these cells was restored by exposure to IGF-1 or analogues with reduced affinity for IGFBP-3 (long Arg3-IGF-1) or IGF1R (Leu24-IGF-1). In EO771 cells implanted orthotopically into mice, hIGFBP-3 expression by the cells inhibited tumor establishment in BP3KO but not wild-type mice. For tumors that successfully established, final weight was not affected significantly by hIGFBP-3 expression. However, final tumor weight was inversely related to intratumoral T cell counts, and sera from BP3KO mice with tumors showed low-titer immunoreactivity against IGFBP-3. The contrasting effects on tumor establishment and progression of IGFBP-3 expressed by mammary carcinoma cells, compared to systemic stromal and circulating IGFBP-3, highlights the complexity of growth regulation by IGFBP-3 in mammary tumors.

Original languageEnglish (US)
Pages (from-to)38-45
Number of pages8
JournalExperimental cell research
Issue number1
StatePublished - Jan 1 2019

All Science Journal Classification (ASJC) codes

  • Cell Biology


  • Breast cancer
  • IGF-1 analogue
  • IGFBP-3
  • Immune response
  • Tumor establishment


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