Placenta growth factor stimulates the growth of Philadelphia chromosome positive acute lymphoblastic leukemia cells by both autocrine and paracrine pathways.
Vascular endothelial growth factor (VEGF) and its associated molecule, placenta growth factor (PlGF) are now known to support normal hematopoiesis, and leukemia cell growth. In this study, expression of VEGF and PlGF in acute lymphoblastic leukemia (ALL) cells was examined by real time reverse transcription-polymerase chain reaction in 20 patient samples. Expression of PlGF was more intense in Philadelphia chromosome positive (Ph(+)) ALL than in Ph(-) ALL cases. On the other hand, expression level of VEGF was not different between Ph(+) and Ph(-) cases. Then, PlGF was added to the two ALL cell lines, CRL1929 (Ph(+)), and Nalm6 (Ph(-)). The PlGF stimulated the growth of CRL1929 in time- and dose-dependent manners, although the growth of Nalm6 was not affected by PlGF. The growth stimulation of CRL1929 by PlGF was confirmed by the increase of S phase cells. And the growth promoting effect of PlGF on CRL1929 was cancelled by simultaneous addition of VEGFR1/Fc (which binds to PlGF and abrogates its function), but was not cancelled by VEGFR2/Fc (which does not bind to PlGF). Then, addition of VEGFR1/Fc to the simple culture of CRL1929 demonstrated growth inhibitory effect. These observations demonstrated that PlGF stimulates the growth of Ph(+) ALL cells by both autocrine and paracrine pathways. Finally, PlGF-VEGFR1 loop might be a therapeutic target to improve the prognosis of Ph(+) ALL.
Ikai
Toshiko
T
Department of Internal Medicine, Division of Haematology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
Miwa
Hiroshi
H
Shikami
Masato
M
Hiramatsu
Akihito
A
Tajima
Emi
E
Yamamoto
Hidesuke
H
Imai
Norikazu
N
Hattori
Akiko
A
Nishii
Kazuhiro
K
Miura
Kazuhisa
K
Satoh
Atsushi
A
Itoh
Masato
M
Imamura
Akira
A
Mihara
Hidetsugu
H
Katoh
Yoshiro
Y
Nitta
Masakazu
M
D019898:Autocrine Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019899:Paracrine Communication / Q000502:physiology*; D000072483:Placenta Growth Factor; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000473:pathology*; D011257:Pregnancy Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000502:physiology
C000608036:PGF protein, human; D011257:Pregnancy Proteins; D012334:RNA, Neoplasm; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1