Enkephalins stimulate leukemia cell migration and surface expression of CD9.
Opioid peptides have been implicated in the regulation of tumor growth and biology; however, little attention has been given to the mechanisms that are involved. In this study we show that physiological concentrations of the endogenous opioid neuropeptide methionine-enkephalin (MET-ENK) and the synthetic enkephalins D-Ala2, Me-Phe4, Gly(ol)5 and D-Ala2, D-Leu5 are stimulants for the in vitro migration of pre-B acute lymphoblastoid leukemia (ALL) cells. Activation of the human pre-B ALL cell lines NALM 6 and LAZ 221 with MET-ENK resulted in both an increase in their migration and an augmentation in the surface expression of the leukemia cell marker CD9. The opiate receptor antagonist naloxone reversed these enkephalin-induced effects on the leukemia cells. When the pre-B ALL cells were preincubated with an anti-CD9 mAb before challenge with MET-ENK their migration to the enkephalin was markedly reduced. These studies show that endogenous and synthetic opioid peptides are stimulants for pre-B ALL cell migration and suggest that CD9 is important in the regulation of leukemia cell motility.
Heagy
W
W
Laboratory of Infectious Diseases, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Duca
K
K
Finberg
R W
RW
D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis*; D002051:Burkitt Lymphoma; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; D060245:Tetraspanin 29; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C554869:CD9 protein, human; D004745:Enkephalins; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29; D004744:Enkephalin, Methionine