Identification of a vascular endothelial growth factor (VEGF) antagonist, sFlt-1, from a human hematopoietic cell line NALM-16.
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.
Inoue
T
T
Fujisaki Cell Center, Hayashibara Biochemical Laboratories, Inc., 675-1 Fujisaki, Okayama, Japan. fcch@hayashibara.co.jp
Kibata
K
K
Suzuki
M
M
Nakamura
S
S
Motoda
R
R
Orita
K
K
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000737:chemistry*; D015153:Blotting, Western; D002460:Cell Line; D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors*; D006410:Hematopoiesis; D006801:Humans; D008222:Lymphokines / Q000037:antagonists & inhibitors*; D008969:Molecular Sequence Data; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000302:isolation & purification* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000302:isolation & purification* / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1