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

Producción científica: Article › revisión exhaustiva

10 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	799-806
Número de páginas	8
Publicación	International Journal of Biological Sciences
Volumen	14
N.º	7
DOI	https://doi.org/10.7150/ijbs.25928
Estado	Published - may 21 2018

Nota bibliográfica

Publisher Copyright:
© Ivyspring International Publisher.

Financiación

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).

Financiadores	Número del financiador
Guangdong Provincial Applied Science and Technology Research and Development Program
Science and Technology Development Fund of Macau	FDCT/ 131/2016/A3
Shenzhen Science and Technology Innovation Committee	SRG2 016-00082-FHS, JCY J20150401145529036, JCYJ20160608140912962, ZDSYS 20140509142721429, JCYJ20160531171744232
National Natural Science Foundation of China (NSFC)
Natural Science Foundation of Guangdong Province	2015A0 30313741
Natural Science Foundation of Guangdong Province
Guangzhou Science and Technology Program key projects	201807010004
Guangzhou Science and Technology Program key projects
Universidade de Macau	31770996, 31670753, 31440041
Universidade de Macau
Fundo para o Desenvolvimento das Ciências e da Tecnologia	131/2016/A3
Fundo para o Desenvolvimento das Ciências e da Tecnologia
Guangdong Science and Technology Department	2017B030301018, 2016A050502034
Guangdong Science and Technology Department

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

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

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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",

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month = may,

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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

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.

KW - Affinity maturation

KW - Insulin-like growth factor

KW - Yeast display

KW - eAd

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M3 - Article

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AN - SCOPUS:85048170274

SN - 1449-2288

VL - 14

SP - 799

EP - 806

JO - International Journal of Biological Sciences

JF - International Journal of Biological Sciences

IS - 7

ER -

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

Resumen

Nota bibliográfica

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

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Huella

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