A novel single-chain variable fragment antibody against FGF-1 inhibits the growth of breast carcinoma cells by blocking the intracrine pathway of FGF-1

Heng-Liang Shi; Tao Yang; Khalissa Deffar; Chun-Guang Dong; Jing-Ying Liu; Chun-Ling Fu; Da-Xue Zheng; Bo Qin; Jun-Jie Wang; Xing-Zhi Wang; Xiao-Juan Zhu

doi:10.1002/iub.423

A novel single-chain variable fragment antibody against FGF-1 inhibits the growth of breast carcinoma cells by blocking the intracrine pathway of FGF-1

IUBMB Life. 2011 Feb;63(2):129-37. doi: 10.1002/iub.423. Epub 2011 Feb 24.

Authors

Heng-Liang Shi¹, Tao Yang, Khalissa Deffar, Chun-Guang Dong, Jing-Ying Liu, Chun-Ling Fu, Da-Xue Zheng, Bo Qin, Jun-Jie Wang, Xing-Zhi Wang, Xiao-Juan Zhu

Affiliation

¹ Key Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Cytology and Genetics, Northeast Normal University, Changchun, China.

PMID: 21360642
DOI: 10.1002/iub.423

Abstract

The fibroblast growth factors (FGFs) are important for embryo development, wound healing, hematopoiesis, and angiogenesis. FGF-1, a member of FGF family, is involved in both receptor-dependent pathways and an intracrine pathway. Studies have recently shown that FGF-1 is overexpressed in the early stages of several kinds of cancer. Thus, FGF-1 is a candidate for cancer immunotargeting. To study the potential use of therapeutic antibodies against FGF-1, a monoclonal hybridoma 1C9 secreting monoclonal antibody specific for FGF-1 was developed. Then, a single-chain variable fragment (scFv) antibody was genetically engineered from hybridama 1C9. The binding of the scFv1C9 to the antigen FGF-1 was demonstrated by ELISA and immunoprecipitation assays. Functional analysis showed that the overexpressed scFv1C9 in MCF-7 cells targeted endogenous FGF-1 and prevented the translocation of FGF-1 into the nucleus, resulting in the blockade of the intracrine pathway of FGF-1, which caused the G1 arrest by p21 up-regulation. These results suggest that the generated scFv1C9 is an effective inhibitor of the intracrine pathway of FGF-1 and has a potential application as anti-tumoral agent in breast cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / immunology
Antineoplastic Agents / pharmacology*
Antineoplastic Agents / therapeutic use
Base Sequence
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism*
Breast Neoplasms / drug therapy
Breast Neoplasms / genetics
Breast Neoplasms / immunology*
Breast Neoplasms / metabolism*
Breast Neoplasms / pathology
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cyclin-Dependent Kinase Inhibitor p21 / genetics
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Escherichia coli
Female
Fibroblast Growth Factor 1 / genetics
Fibroblast Growth Factor 1 / metabolism*
Gene Expression
Humans
Hybridomas / chemistry
Hybridomas / metabolism
Immunomodulation
Mice
Molecular Sequence Data
Molecular Targeted Therapy / methods
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Signal Transduction / drug effects*
Single-Chain Antibodies / immunology
Single-Chain Antibodies / pharmacology*
Single-Chain Antibodies / therapeutic use
Up-Regulation

Substances

Antineoplastic Agents
Biomarkers, Tumor
CDKN1A protein, human
Cyclin-Dependent Kinase Inhibitor p21
Recombinant Proteins
Single-Chain Antibodies
Fibroblast Growth Factor 1