Identification of a vascular endothelial growth factor (VEGF) antagonist, sFlt-1, from a human hematopoietic cell line NALM-16

被引:31
作者
Inoue, T [1 ]
Kibata, K [1 ]
Suzuki, M [1 ]
Nakamura, S [1 ]
Motoda, R [1 ]
Orita, K [1 ]
机构
[1] Hayashibara Biochem Labs Inc, Fujisaki Cell Ctr, Okayama 7028006, Japan
关键词
vascular endothelial growth factor; Flt-1; antagonist; hematopoietic cell;
D O I
10.1016/S0014-5793(00)01246-1
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
An antagonistic activity against vascular endothelial growth factor (VEGF) was identified in the culture supernatants of certain human hematopoietic cell lines and the antagonistic protein was purified from NALM-16 (B cell) culture supernatant, Amino acid sequencing of the N-terminus and Western blot analysis confirmed that the antagonist was identical to a soluble truncated form of Flt-1 (sFlt-1), Seventeen of 52 leukemia and lymphoma cell lines investigated expressed sFlt-1 mRNA, and 16 of the sFlt-1 expressing cells also expressed VEGF and membrane-bound Flt-1 (mFlt-1). This report is the first showing that sFlt-1 can be produced by malignant hematopoietic cells, suggesting that the production of VEGF antagonist by hematopoietic cells may play some role in the regulation of VEGF activity in normal and malignant hematopoietic cell proliferation. (C) 2000 Federation of European Biochemical Societies.
引用
收藏
页码:14 / 18
页数:5
相关论文
共 16 条
[1]   MOLECULAR AND BIOLOGICAL PROPERTIES OF THE VASCULAR ENDOTHELIAL GROWTH-FACTOR FAMILY OF PROTEINS [J].
FERRARA, N ;
HOUCK, K ;
JAKEMAN, L ;
LEUNG, DW .
ENDOCRINE REVIEWS, 1992, 13 (01) :18-32
[2]   ANGIOGENESIS IN CANCER, VASCULAR, RHEUMATOID AND OTHER DISEASE [J].
FOLKMAN, J .
NATURE MEDICINE, 1995, 1 (01) :27-31
[3]   Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells [J].
Gabrilovich, DI ;
Chen, HL ;
Cunningham, HT ;
Meny, GM ;
Nadaf, S ;
Kavanaugh, D ;
Carbone, DP .
NATURE MEDICINE, 1996, 2 (10) :1096-1103
[4]   Paracrine expression of a native soluble vascular endothelial growth factor receptor inhibits tumor growth, metastasis, and mortality rate [J].
Goldman, CK ;
Kendall, RL ;
Cabrera, G ;
Soroceanu, L ;
Heike, Y ;
Gillespie, GY ;
Siegal, GP ;
Mao, XZ ;
Bett, AJ ;
Huckle, WR ;
Thomas, KA ;
Curiel, DT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (15) :8795-8800
[5]  
KATOH O, 1995, CANCER RES, V55, P5687
[6]   Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR [J].
Kendall, RL ;
Wang, G ;
Thomas, KA .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 226 (02) :324-328
[7]  
KOHNO S, 1980, J NATL CANCER I, V64, P485
[8]   Establishment and characterization of human B cell precursor leukemia cell lines [J].
Matsuo, Y ;
Drexler, HG .
LEUKEMIA RESEARCH, 1998, 22 (07) :567-579
[9]   HIGH-AFFINITY VEGF BINDING AND DEVELOPMENTAL EXPRESSION SUGGEST FLK-1 AS A MAJOR REGULATOR OF VASCULOGENESIS AND ANGIOGENESIS [J].
MILLAUER, B ;
WIZIGMANNVOOS, S ;
SCHNURCH, H ;
MARTINEZ, R ;
MOLLER, NPH ;
RISAU, W ;
ULLRICH, A .
CELL, 1993, 72 (06) :835-846
[10]  
MOHLE R, 1997, P NATL ACAD SCI USA, V94, P6663