THE BINDING OF HB-EGF TO TUMOR-CELLS IS BLOCKED BY MABS WHICH ACT AS EGF AND TGF-ALPHA ANTAGONISTS

被引:13
作者
MODJTAHEDI, H [1 ]
DEAN, C [1 ]
机构
[1] INST CANC RES,IMMUNOL SECT,SUTTON SM2 5NG,SURREY,ENGLAND
关键词
D O I
10.1006/bbrc.1995.1200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Heparin binding EGF (HB-EGF), a newly discovered member of the EGF family of mitogens, binds to the EGF receptor (EGFR) and to heparan sulfate proteoglycans on the cell surface. Here, we show that the binding of HB-EGF to the EGFR is inhibited by mAbs which prevent the interaction of EGF and TGF alpha with the receptor. Also, we show that, like EGF and TGF alpha, treatment with HB-EGF inhibits the growth in vitro of tumours (HN5, HSC-4) that overexpress the EGFR. We conclude that mAbs which act as EGF and TGF alpha antagonists should also be effective therapeutic agents for blocking the growth of EGFR overexpressing tumours induced by HB-EGF. (C) 1995 Academic Press, Inc.
引用
收藏
页码:389 / 397
页数:9
相关论文
共 34 条
[1]   HEPARIN-BINDING EGF-LIKE GROWTH-FACTOR - CHARACTERIZATION OF RAT AND MOUSE CDNA CLONES, PROTEIN DOMAIN CONSERVATION ACROSS SPECIES, AND TRANSCRIPT EXPRESSION IN TISSUES [J].
ABRAHAM, JA ;
DAMM, D ;
BAJARDI, A ;
MILLER, J ;
KLAGSBRUN, M ;
EZEKOWITZ, RAB .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 190 (01) :125-133
[2]   HEPARIN-DEPENDENT BINDING AND AUTOPHOSPHORYLATION OF EPIDERMAL GROWTH-FACTOR (EGF) RECEPTOR BY HEPARIN-BINDING EGF-LIKE GROWTH-FACTOR BUT NOT BY EGF [J].
AVIEZER, D ;
YAYON, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (25) :12173-12177
[4]   ISOLATION AND CHARACTERIZATION OF A MACROPHAGE-DERIVED HEPARIN-BINDING GROWTH-FACTOR [J].
BESNER, G ;
HIGASHIYAMA, S ;
KLAGSBRUN, M .
CELL REGULATION, 1990, 1 (11) :811-819
[5]   Interaction of Heparin-Binding EGF-Like Growth Factor (HB-EGF) with the Epidermal Growth Factor Receptor: Modulation by Heparin, Heparinase, or Synthetic Heparin-Binding HB-EGF Fragments [J].
Besner, Gail E. ;
Whelton, Diane ;
Crissman-Combs, Melissa A. ;
Steffen, Christy L. ;
Kim, Gregory Y. ;
Brigstock, David R. .
GROWTH FACTORS, 1992, 7 (04) :289-296
[6]   T-LYMPHOCYTES SYNTHESIZE AND EXPORT HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH-FACTOR AND BASIC FIBROBLAST GROWTH-FACTOR, MITOGENS FOR VASCULAR CELLS AND FIBROBLASTS - DIFFERENTIAL PRODUCTION AND RELEASE BY CD4+ AND CD8+ T-CELLS [J].
BLOTNICK, S ;
PEOPLES, GE ;
FREEMAN, MR ;
EBERLEIN, TJ ;
KLAGSBRUN, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (08) :2890-2894
[7]  
CARPENTER G, 1990, J BIOL CHEM, V256, P7709
[8]  
COHEN S, 1962, J BIOL CHEM, V237, P1555
[9]  
Cowley GO, 1984, CANCER CELL, V1, P5
[10]   SPECIFIC RADIOLABELING OF A CELL-SURFACE RECEPTOR FOR EPIDERMAL GROWTH-FACTOR [J].
DAS, M ;
MIYAKAWA, T ;
FOX, CF ;
PRUSS, RM ;
AHARONOV, A ;
HERSCHMAN, HR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1977, 74 (07) :2790-2794