A dual-specific IGF-I/II human engineered antibody domain inhibits IGF signaling in breast cancer cells

Int J Biol Sci. 2018 May 21;14(7):799-806. doi: 10.7150/ijbs.25928. eCollection 2018.

Abstract

The insulin-like growth factors (IGFs), IGF-I and IGF-II, are essential for regulating cell growth, differentiation and metastasis of a broad range of malignancies. The IGF-I/II actions are mediated through the IGF receptor type 1 (IGF-1R) and the insulin receptor (IR), which are overexpressed in multiple types of tumors. Here, we have firstly identified a human engineered antibody domain (eAd) from a phage-displayed VH library. The eAd suppressed the signal transduction of IGF-1R mediated by exogenous IGF-I or IGF-II in breast cancer cell lines through neutralizing both IGF-I and IGF-II. It also significantly inhibited the growth of breast cancer cells. Therefore, the anti-IGF-I/II eAd offers an alternative approach to target both the IGF-1R signaling pathways through the inhibition of IGF-I/II.

Keywords: Affinity maturation; Insulin-like growth factor; Yeast display; eAd.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor II / metabolism*
  • Phosphorylation / genetics
  • Phosphorylation / physiology
  • Signal Transduction

Substances

  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II