A Recombinant Decoy Comprising EGFR and ErbB-4 Inhibits Tumor Growth and Metastasis

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2011 Nov 23

PMID 22105361

Citations 19

Authors

M Lindzen

S Carvalho

A Starr

N Ben-Chetrit

C-R Pradeep

W J Kostler

A Rabinkov

S Lavi

S S Bacus

Y Yarden

Affiliations

Soon will be listed here.

Abstract

Epidermal growth factor (EGF)-like growth factors control tumor progression as well as evasion from the toxic effects of chemotherapy. Accordingly, antibodies targeting the cognate receptors, such as EGFR/ErbB-1 and the co-receptor HER2/ErbB-2, are widely used to treat cancer patients, but agents that target the EGF-like growth factors are not available. To circumvent the existence of 11 distinct ErbB ligands, we constructed a soluble fusion protein (hereinafter: TRAP-Fc) comprising truncated extracellular domains of EGFR/ErbB-1 and ErbB-4. The recombinant TRAP-Fc retained high-affinity ligand binding to EGF-like growth factors and partially inhibited growth of a variety of cultured tumor cells. Consistently, TRAP-Fc displayed an inhibitory effect in xenograft models of human cancer, as well as synergy with chemotherapy. Additionally, TRAP-Fc inhibited invasive growth of mammary tumor cells and reduced their metastatic seeding in the lungs of animals. Taken together, the activities displayed by TRAP-Fc reinforce critical roles of EGF-like growth factors in tumor progression, and they warrant further tests of TRAP-Fc in preclinical models.

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