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

doi:10.7150/ijbs.25928

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

Biostatistics

Research output: Contribution to journal › Article › peer-review

8 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 language	English
Pages (from-to)	799-806
Number of pages	8
Journal	International Journal of Biological Sciences
Volume	14
Issue number	7
DOIs	https://doi.org/10.7150/ijbs.25928
State	Published - 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
Insulin-like growth factor
Yeast display
eAd

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.7150/ijbs.25928

Cite this

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

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",

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

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: {\textcopyright} Ivyspring International Publisher.",

year = "2018",

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doi = "10.7150/ijbs.25928",

language = "English",

volume = "14",

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AU - Chen, Zhizhen

AU - Liu, Jie

AU - Chu, Dafeng

AU - Shan, Yaming

AU - Ma, Guixing

AU - Zhang, Hongmin

AU - Zhang, Xiaohua Douglas

AU - Wang, Pu

AU - Chen, Qiang

AU - Deng, Chuxia

AU - Chen, Weizao

AU - Dimitrov, Dimiter S.

AU - Zhao, Qi

N1 - 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.

PY - 2018/5/21

Y1 - 2018/5/21

N2 - 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.

AB - 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.

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KW - Insulin-like growth factor

KW - Yeast display

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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