Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration.
Multiple myeloma (MM) remains incurable, with a median survival of 3 to 4 years. This study shows direct effects of vascular endothelial growth factor (VEGF) upon MM and plasma cell leukemia (PCL) cells. The results indicate that VEGF triggers tumor cell proliferation via a protein kinase C (PKC)-independent Raf-1-MEK-extracellular signal-regulated protein kinase pathway, and migration via a PKC-dependent pathway. These observations provide the framework for novel therapeutic strategies targeting VEGF signaling cascades in MM.
Podar
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Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Tai
Y T
YT
Davies
F E
FE
Lentzsch
S
S
Sattler
M
M
Hideshima
T
T
Lin
B K
BK
Gupta
D
D
Shima
Y
Y
Chauhan
D
D
Mitsiades
C
C
Raje
N
N
Richardson
P
P
Anderson
K C
KC
D002455:Cell Division / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D007952:Leukemia, Plasma Cell / Q000378:metabolism / Q000473:pathology; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D048369:MAP Kinase Kinase 1; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D016326:Extracellular Matrix Proteins; D005419:Flavonoids; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one