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.

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.

• Authors: 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
• Journal: IUBMB life (IUBMB Life) Vol. 63 Issue 2 Pg. 129-37 (Feb 2011) ISSN: 1521-6551 [Electronic] England
• PMID: 21360642 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley Periodicals, Inc.

Chemical References

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

Topics

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