Lysophosphatidic acid receptor expression in chronic lymphocytic leukemia leads to cell survival mediated though vascular endothelial growth factor expression.
Lysophosphatidic acid (LPA) protects chronic lymphocytic leukemia (CLL) cells from apoptosis. Vascular endothelial growth factor (VEGF) also protects CLL cells against apoptosis. The mechanism for LPA protection against apoptosis in CLL cells is unknown. Herein, we show CLL cells express LPA receptors LPA(1-5) but in normal B cells, LPA(1) was rarely expressed and LPA(3,) LPA(4,) and LPA(6) were undetectable whereas the other LPA receptors were expressed. LPA plasma levels are similar in patients with CLL compared to healthy controls. In contrast, plasma levels of VEGF are elevated in patients with CLL compared to healthy controls and LPA treatment induced VEGF secretion in CLL cells. CLL cells also express VEGF receptors and LPA protection against Flu induced apoptosis is blocked by inhibition of VEGF receptor activation. These results indicate that LPA protects CLL cells from apoptosis through higher expression of LPA receptors and autocrine production of VEGF.
Kumar
Sekar Ashok
SA
Manitoba Institute of Cell Biology, Winnipeg, MB, Canada.
Hu
Xiaojie
X
Brown
Michelle
M
Kuschak
Brenda
B
Hernandez
Tiffany A
TA
Johnston
James B
JB
Gibson
Spencer B
SB
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008246:Lysophospholipids / Q000097:blood / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics*; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D014740:Vidarabine / Q000031:analogs & derivatives / Q000494:pharmacology
C082320:LPAR4 protein, human; C512992:LPAR5 protein, human; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D018048:Receptors, Purinergic P2; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor; D014740:Vidarabine; C024352:fludarabine; C032881:lysophosphatidic acid