CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung.
Bombesin-like peptides are essential autocrine growth factors for many small cell carcinomas (SCCas) of the lung. Herein, we demonstrate that these malignant pulmonary neuroendocrine cells express low levels of the cell surface metalloendopeptidase CD10/neutral endopeptidase 24.11 (CD10/NEP, common acute lymphoblastic leukemia antigen) and that this enzyme hydrolyzes bombesin-like peptides. The growth of bombesin-like peptide-dependent SCC as is inhibited by CD10/NEP and potentiated by CD10/NEP inhibition. The results provide evidence that CD10/NEP is involved in the regulation of tumor cell proliferation. Since SCCa of the lung occurs almost exclusively in cigarette smokers and cigarette smoke inactivates CD10/NEP, decreased cell surface CD10/NEP enzymatic activity may be causally related to the development of SCCa of the lung.
Shipp
M A
MA
Department of Medicine, Harvard Medical School, Boston, MA 02115.
Tarr
G E
GE
Chen
C Y
CY
Switzer
S N
SN
Hersh
L B
LB
Stein
H
H
Sunday
M E
ME
Reinherz
E L
EL
D000595:Amino Acid Sequence; D000943:Antigens, Differentiation / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001839:Bombesin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000201:enzymology / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication; D005333:Fetus; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D008168:Lung / Q000166:cytology / Q000196:embryology / Q000201:enzymology; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology*; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000378:metabolism*; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors; D013379:Substrate Specificity
D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D006020:Glycopeptides; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter; D015260:Neprilysin; D001839:Bombesin; C008890:phosphoramidon