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Placenta growth factor stimulates the growth of Philadelphia chromosome positive acute lymphoblastic leukemia cells by both autocrine and paracrine pathways
Author(s) -
Ikai Toshiko,
Miwa Hiroshi,
Shikami Masato,
Hiramatsu Akihito,
Tajima Emi,
Yamamoto Hidesuke,
Imai Norikazu,
Hattori Akiko,
Nishii Kazuhiro,
Miura Kazuhisa,
Satoh Atsushi,
Itoh Masato,
Imamura Akira,
Mihara Hidetsugu,
Katoh Yoshiro,
Nitta Masakazu
Publication year - 2005
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2005.00505.x
Subject(s) - autocrine signalling , paracrine signalling , placental growth factor , cancer research , medicine , vascular endothelial growth factor , growth factor , endocrinology , receptor , vegf receptors
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.