CD10/neutral endopeptidase 24.11 in developing human fetal lung. Patterns of expression and modulation of peptide-mediated proliferation.
TLDR
The specific BLP receptor antagonist, [Leu13-psi(CH2NH)Leu14]bombesin abolishes these effects on fetal lung growth, suggesting that CD10/NEP modulates BLP-mediated proliferation.Abstract:
The cell membrane-associated enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) functions in multiple organ systems to downregulate responses to peptide hormones. Recently, CD10/NEP was found to hydrolyze bombesin-like peptides (BLP), which are mitogens for normal bronchial epithelial cells and small cell lung carcinomas. Growth of BLP-responsive small cell lung carcinomas was potentiated by CD10/NEP inhibition, implicating CD10/NEP in regulation of BLP-mediated tumor growth. BLP are also likely to participate in normal lung development because high BLP levels are found in fetal lung, and bombesin induces proliferation and maturation of human fetal lung in organ cultures and murine fetal lung in utero. To explore potential roles for CD10/NEP in regulating peptide-mediated human fetal lung development, we have characterized temporal and cellular patterns of CD10/NEP expression and effects of CD10/NEP inhibition in organ cultures. Peak CD10/NEP transcript levels are identified at 11-13 wk gestation by Northern blots and localized to epithelial cells and mesenchyme of developing airways by in situ hybridization. CD10/NEP immunostaining is most intense in undifferentiated airway epithelium. In human fetal lung organ cultures, inhibition of CD10/NEP with either phosphoramidon or SCH32615 increases thymidine incorporation by 166-182% (P < 0.025). The specific BLP receptor antagonist, [Leu13-psi(CH2NH)Leu14]bombesin abolishes these effects on fetal lung growth, suggesting that CD10/NEP modulates BLP-mediated proliferation. CD10/NEP expression in the growing front of airway epithelium and the effects of CD10/NEP inhibitors in lung explants implicate the enzyme in the regulation of peptide-mediated fetal lung growth.read more
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Journal ArticleDOI
Neutral endopeptidase 24.11 loss in metastatic human prostate cancer contributes to androgen-independent progression.
Christos N. Papandreou,B A Usmani,Yiping Geng,Thomas Bogenrieder,Ronald H. Freeman,Wilk S,Connie L. Finstad,Victor E. Reuter,Powell Ct,David A. Scheinberg,Magill C,Howard I. Scher,Anthony P. Albino,David M. Nanus +13 more
TL;DR: It is suggested that NEP loss plays an important role in the development of androgen-independent PC by allowing PC cells to use mitogenic neuropeptides as an alternate source to androgen in order to stimulate cell proliferation.
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Molecular pathogenesis of lung cancer.
TL;DR: Efforts are ongoing to translate findings of abnormalities of proto-oncogenes, genetic and epigenetic changes of tumor suppressor genes, the role of angiogenesis in the multistage development of lung cancer, as well as detection of molecular abnormalities in preinvasive respiratory lesions into new clinical strategies.
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Sex-Specific Expression of Gastrin-Releasing Peptide Receptor: Relationship to Smoking History and Risk of Lung Cancer
Sharon P. Shriver,Heather A. Bourdeau,Christopher T. Gubish,Dayna L. Tirpak,Autumn Gaither Davis,James D. Luketich,Jill M. Siegfried +6 more
TL;DR: The results suggest that the GRPR gene is expressed more frequently in women than in men in the absence of smoking and that expression of this gene is activated earlier in women in response to tobacco exposure.
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Concise review: neutral endopeptidase (CD10): a multifaceted environment actor in stem cells, physiological mechanisms, and cancer.
Véronique Maguer-Satta,Véronique Maguer-Satta,Roger Besançon,Elodie Bachelard-Cascales,Elodie Bachelard-Cascales +4 more
TL;DR: CD10 is not only a cell surface marker in normal and malignant contexts but also affects the extracellular environment and plays a key role in regulation of a number of biological functions and likely in SC.
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Molecular Pathogenesis of Lung Cancer
TL;DR: Because the molecular alterations are known, new mechanism-based therapies are being developed and brought to the clinic, including new drugs, vaccines, and gene therapy, which also must be integrated with standard therapies.
References
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