| First Author | Scully T | Year | 2019 |
| Journal | Exp Cell Res | Volume | 374 |
| Issue | 1 | Pages | 38-45 |
| PubMed ID | 30419192 | Mgi Jnum | J:269792 |
| Mgi Id | MGI:6271549 | Doi | 10.1016/j.yexcr.2018.11.006 |
| Citation | Scully T, et al. (2019) Contrasting effects of IGF binding protein-3 expression in mammary tumor cells and the tumor microenvironment. Exp Cell Res 374(1):38-45 |
| abstractText | 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 Arg(3)-IGF-1) or IGF1R (Leu(24)-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. |
