The FGF-1-specific single-chain antibody scFv1C9 effectively inhibits breast cancer tumour growth and metastasis.

Abstract

Immunotherapy mediated by recombinant antibodies is an effective therapeutic strategy for a variety of cancers. In a previous study, we demonstrated that the fibroblast growth factor 1 (FGF-1)-specific recombinant antibody scFv1C9 arrests the cell cycle at the G0/G1 transition by blocking the intracrine FGF-1 pathway in breast cancer cells. Here, we further show that the overexpression of scFv1C9 in MCF-7 and MDA-MB-231 breast cancer cells by lentiviral infection resulted in decreased tumourigenicity, tumour growth and lung metastasis through FGF-1 neutralization. We found that scFv1C9 resulted in the up-regulation of p21, which in turn inhibited the expression of CDK2 and blocked cell cycle progression. To explore the potential role of scFv1C9 in vivo, we delivered the gene into solid tumours by electroporation, which resulted in significant inhibition of tumour growth. In tumour tissue sections, immunohistochemical staining of the cellular proliferation marker Ki-67 and the microvessel marker CD31 showed a reduction in the proliferative index and microvessel density, respectively, upon expression of scFv1C9 compared with the appropriate controls. Thus, our data indicate a central role for scFv1C9 in blocking the intracrine pathway of FGF-1, therefore, scFv1C9 could be developed in an effective therapeutic for breast cancer.

• Authors: Hengliang Shi, Chunling Fu, Wei Wang, Yu Li, Shuang Du, Rangjuan Cao, Jingying Chen, Dong Sun, Zhongyu Zhang, Xingzhi Wang, Xiaojuan Zhu
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 18 Issue 10 Pg. 2061-70 (Oct 2014) ISSN: 1582-4934 [Electronic] England
• PMID: 25124967 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• RNA, Small Interfering
• Single-Chain Antibodies
• Fibroblast Growth Factor 1

Topics

• Animals
• Blotting, Western
• Breast Neoplasms (metabolism, pathology, prevention & control)
• Cell Cycle
• Cell Proliferation
• Female
• Fibroblast Growth Factor 1 (antagonists & inhibitors, genetics, immunology)
• Humans
• Immunoenzyme Techniques
• Lung Neoplasms (metabolism, prevention & control, secondary)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred NOD
• Mice, Nude
• Mice, SCID
• RNA, Small Interfering (genetics)
• Single-Chain Antibodies (therapeutic use)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays