Somatostatin induces migration of acute myeloid leukemia cells via activation of somatostatin receptor subtype 2.
Somatostatin, a neuropeptide with multiple activities, exerts its function via G-coupled membrane receptors. Five somatostatin receptor subtypes, sst1-5, have been identified. We have recently established that somatostatin acts as a chemoattractant on normal hematopoietic progenitor cells. Here, we studied the expression of somatostatin receptors (sst) on leukemic cells from 16 AML patients. Using fluorescent somatostatin (Fluo-SS) in flow cytometry, we found that sst are expressed in variable amounts on primary AML cells. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis and immunochemistry revealed that only sst subtype 2 is expressed by AML cells. Using a two-chamber in vitro migration assay, we show that AML cells migrated towards a gradient of octreotide, a stable synthetic analogue of somatostatin. The degree of migration correlated with the cell surface density of sst2 as measured by Fluo-SS binding. These findings indicate that somatostatin influences trafficking of AML cells, which may have implications for the distribution of AML cells in the body and for clinical applications of somatostatin and analogues thereof in the context of AML.
Oomen
S P
SP
Institute of Hematology, Dr Daniel den Hoed Cancer Center, Erasmus University, Rotterdam, The Netherlands.
Lichtenauer-Kaligis
E G
EG
Verplanke
N
N
Hofland
J
J
Lamberts
S W
SW
Löwenberg
B
B
Touw
I P
IP
D001854:Bone Marrow Cells / Q000502:physiology; D002465:Cell Movement; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D015282:Octreotide / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000032:analysis / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000032:analysis / Q000502:physiology*
D017481:Receptors, Somatostatin; D013004:Somatostatin; C093733:somatostatin receptor 2; D015282:Octreotide