Lysophosphatidic acid receptor expression in chronic lymphocytic leukemia leads to cell survival mediated though vascular endothelial growth factor expression

Sekar Ashok Kumar; Xiaojie Hu; Michelle Brown; Brenda Kuschak; Tiffany A Hernandez; James B Johnston; Spencer B Gibson

doi:10.3109/10428190903275586

Lysophosphatidic acid receptor expression in chronic lymphocytic leukemia leads to cell survival mediated though vascular endothelial growth factor expression

Leuk Lymphoma. 2009 Dec;50(12):2038-48. doi: 10.3109/10428190903275586.

Authors

Sekar Ashok Kumar¹, Xiaojie Hu, Michelle Brown, Brenda Kuschak, Tiffany A Hernandez, James B Johnston, Spencer B Gibson

Affiliation

¹ Manitoba Institute of Cell Biology, Winnipeg, MB, Canada.

PMID: 19860625
DOI: 10.3109/10428190903275586

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Apoptosis / drug effects
Cell Line, Tumor
Cell Survival / drug effects
Cells, Cultured
Female
Gene Expression Profiling
Humans
Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
Leukemia, Lymphocytic, Chronic, B-Cell / pathology
Lysophospholipids / blood
Lysophospholipids / pharmacology
Male
Middle Aged
Receptors, Lysophosphatidic Acid / genetics*
Receptors, Purinergic P2 / genetics*
Receptors, Vascular Endothelial Growth Factor / genetics*
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects
Vascular Endothelial Growth Factor A / blood*
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / metabolism
Vidarabine / analogs & derivatives
Vidarabine / pharmacology

Substances

LPAR4 protein, human
LPAR5 protein, human
Lysophospholipids
Receptors, Lysophosphatidic Acid
Receptors, Purinergic P2
Vascular Endothelial Growth Factor A
Receptors, Vascular Endothelial Growth Factor
Vidarabine
fludarabine
lysophosphatidic acid