Neuropilin-1 in acute myeloid leukemia: expression and role in proliferation and migration of leukemia cells.
Neuropilin-1 (NRP-1) is a novel receptor of vascular endothelial growth factor (VEGF) and expressed in endothelial cells and tumor cells. The role of NRP-1 in the growth and progression of leukemia is unknown. Here we studied the mRNA expression and effect of NRP-1 in leukemic cells. Our results showed that NRP-1 mRNA was expressed in six of seven leukemic cell lines and primary leukemias derived from all 24 patients with acute myeloid leukemia (AML). Reduced NRP-1 expression by RNA interference led to a decrease of VEGF-mediated mitogenic and migration responses in acute myeloid leukemic cell line HEL. Increased NRP-1 expression was directly correlated with the blast percentage in both peripheral blood and bone marrow of AML patients. Our data demonstrated that a higher level of NRP-1 mRNA was expressed in leukemias and NRP-1 promoted proliferation and chemotaxis of leukemic cells in response to VEGF. Inhibition of NRP-1 functions may provide a new therapeutic strategy for treatment of AML.
Lu
Lin
L
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People's Republic of China.
Zhang
Lei
L
Xiao
Zhijian
Z
Lu
Shihong
S
Yang
Renchi
R
Han
Zhong Chao
ZC
D000293:Adolescent; D000328:Adult; D000368:Aged; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002633:Chemotaxis; D002648:Child; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D039942:Neuropilin-1 / Q000032:analysis* / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D012333:RNA, Messenger; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1