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

Zhizhen Chen, Jie Liu, Dafeng Chu, Yaming Shan, Guixing Ma, Hongmin Zhang, Xiaohua Douglas Zhang, Pu Wang, Qiang Chen, Chuxia Deng, Weizao Chen, Dimiter S. Dimitrov, Qi Zhao

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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.

Original languageEnglish
Pages (from-to)799-806
Number of pages8
JournalInternational Journal of Biological Sciences
Volume14
Issue number7
DOIs
StatePublished - May 21 2018

Bibliographical note

Funding Information:
This work was supported by the Science and Technology Development Fund of Macau (FDCT/ 131/2016/A3), the Guangdong Science and Technology Program (2016A050502034 and 2017B030301018), the Guangzhou Science and Technology Program (201807010004), Natural Science Foundation of Guangdong (2015A0 30313741), Shenzhen Science and Technology Innovation Committee (JCYJ20160531171744232, JCY J20150401145529036, JCYJ20160608140912962, ZDSYS 20140509142721429), Start-up Research Grand (SRG2 016-00082-FHS) and the intramural research program of Faculty of Health Sciences, University of Macau, and National Natural Science Foundation of China (31440041, 31670753, 31770996).

Publisher Copyright:
© Ivyspring International Publisher.

Keywords

  • Affinity maturation
  • eAd
  • Insulin-like growth factor
  • Yeast display

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'A dual-specific IGF-I/II human engineered antibody domain inhibits IGF signaling in breast cancer cells'. Together they form a unique fingerprint.

Cite this