Breast cancer cell-associated endopeptidase EC 24.11 modulates proliferative response to bombesin

Burns, Deirdre; Walker, Brian; Gray, J.; Nelson, Jane

doi:10.1038/sj.bjc.6690036

Cited by 25 publications

(18 citation statements)

References 66 publications

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“…These findings demonstrate a physiological role of NEP in the function of the human endometrium. NEP can also regulate peptide-mediated cellular proliferation by inactivating bombesin or other neuropeptides that are autocrine or paracrine growth factors for certain solid tumors such as lung, breast, and prostate cancers [6, 7, 8, 9, 10]. These findings suggest that decrease or loss of NEP in carcinoma cells in comparison with normal cellular counterparts results in an increase of bioactive peptides, which in turn disrupts normal cellular homeostasis.…”

Section: Introductionmentioning

confidence: 90%

Imbalance between Neutral Endopeptidase 24.11 and Endothelin-1 Expression in Human Endometrial Carcinoma

Suzuki

Kikkawa²,

Ino³

et al. 2001

Oncology

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Objectives: Neutral endopeptidase 24.11 (NEP)/CD10 is a cell-surface peptidase that degrades various bioactive peptides including endothelin-1 (ET-1). This enzyme is known to play a role in maintaining ET-1-regulated vascular homeostasis in the normal human endometrium. The purpose of the present study was to investigate the expression and localization of NEP and ET-1 in neoplastic endometria, and also to clarify the correlation of their expression with the tumor grade of endometrial carcinoma. Methods: Immunohistochemical analysis for NEP and ET-1 expression was performed on paraffin-embedded tissue sections of 7 normal endometria (after menopause), 5 atypical endometrial hyperplasias (AEH), and 32 endometrial endometrioid adenocarcinomas. Results: In normal endometrium and AEH, NEP immunoreactivity was detected in stromal cells, but not in glandular cells. In contrast, ET-1 immunoreactivity was detected in both glandular and stromal cells. In the stromal cells of grade 1 endometrial adenocarcinoma, NEP was detected at high or moderate quantities. However, significantly decreased NEP immunoreactivity was observed in the stromal cells of grade 2 and 3 adenocarcinomas. However, NEP was not immunostained in adenocarcinoma cells except for the lesions of squamous differentiation. ET-1 immunoreactivity was weakly detected in the stromal cells of grade 1 adenocarcinoma, but the intensity of ET-1 staining increased with advancing tumor grade. The ratio of the staining scores of stromal ET-1 to stromal NEP was positively correlated with the tumor grade. Conclusions: These findings demonstrate that NEP expression in the stromal cells of endometrial adenocarcinoma is downregulated, while stromal ET-1 is upregulated, with increasing tumor grade. The present findings also suggest that NEP may play a role in the regulation of neoplastic transformation, tumor progression, and differentiation in endometrial neoplasms, possibly by degrading certain peptide growth factors such as ET-1.

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Section: Introductionmentioning

confidence: 90%

Imbalance between Neutral Endopeptidase 24.11 and Endothelin-1 Expression in Human Endometrial Carcinoma

Suzuki

Kikkawa²,

Ino³

et al. 2001

Oncology

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“…17 We have also shown that bombesin exerts its mitogenic action in gastric cancer by functionally binding to GRP-R and activating the intracellular calcium [Ca 2ϩ ] pathway. 18 Others have shown the trophic effects of GRP on breast 19 and prostate cancer cell lines. 20,21 Moreover, Cuttitta et al 12 have shown that GRP is an autocrine growth factor for human small cell lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Gastrin-Releasing Peptide Is a Growth Factor for Human Neuroblastomas

Kim¹,

Hu²,

Kelly³

et al. 2002

Annals of Surgery

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ObjectiveTo evaluate whether gastrin-releasing peptide (GRP) and GRP receptor (GRP-R) expression correlate with tumor behavior and to examine the mitogenic actions of GRP on neuroblastomas. Summary Background DataNeuroblastoma is the most common solid tumor of infants and children. Despite recent advances in multimodality treatment regimens, the survival for advanced-stage tumors remains dismal. Neuroblastomas are known to produce GRP; however, the proliferative effects of GRP on neuroblastomas have not been elucidated. MethodsSections of paraffin-embedded neuroblastomas from 33 patients were analyzed for GRP and GRP-R protein expression by immunohistochemistry. Functional binding of GRP-R to the Ca 2ϩ signaling pathway was examined. In addition, the proliferative effect of GRP on neuroblastoma cells (SK-N-SH, IMR-32, SH-SY5Y, LAN-1) was determined. ResultsImmunohistochemical analysis showed GRP and GRP-R protein expression in neuroblastomas; an increased expression of GRP-R was noted in a higher percentage of undifferentiated tumors compared with tumors that were benign. GRP-R mRNA was confirmed in neuroblastoma cell lines. GRP treatment resulted in intracellular calcium [Ca 2ϩ ] i mobilization in two cell lines (SK-N-SH, LAN-1). GRP treatment stimulated growth of all four neuroblastoma cell lines; this effect was inhibited in SK-N-SH cells by pretreatment with GRP antibody. ConclusionsThese findings show increased GRP-R expression in the more aggressive and undifferentiated neuroblastomas. The synchronous expression of GRP and its receptor, GRP-R, suggests a role for these proteins in tumor growth. Moreover, these findings show enhanced proliferation of neuroblastoma cells in vitro after GRP treatment, suggesting that GRP may act as an autocrine and/or paracrine growth factor for neuroblastomas. Treatment with specific GRP-R antagonists may provide novel adjuvant therapy for neuroblastomas in children.

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“…CD10 expression has been reported on epithelial cells of various tissues, such as bronchial epithelial cells, renal proximal tubular epithelial cells, small intestinal epithelium, biliary canaliculae (Loke et al, 1990), breast myoepithelium (O'Hare et al, 1991), prostate, endometrium (Suzuki et al, 2001) and placenta (Ino et al, 2000). Several reports have shown that CD10 is also expressed in selected solid tumours of the colon (Fujimoto et al, 2005), lung (Cohen et al, 1996), breast (Burns et al, 1999), prostate (Dai et al, 2001) and ovary .…”

Section: Cd157/ Bst1mentioning

confidence: 99%

“…Apart from the hematopoietic compartment, CD10 participates in the final stage of peptide hydrolysis in the renal proximal tubules and the small intestine. Several reports showed that CD10 plays a role in neoplastic transformation and tumour progression in selected human malignancies by inactivating ET-1 or bombesin, both involved in autocrine/paracrine stimulation of tumour cell proliferation and migration in many epithelial cancers, including breast (Burns, et al, 1999), lung (Cohen, et al, 1996) and prostate cancers (Dai, et al, 2001). CD10 is expressed in the stroma of malignant ovarian carcinomas, but not in benign adenomas or in normal ovaries, and its expression inversely correlates with histologic tumour grade .…”

Section: Functionsmentioning

confidence: 99%

Ectoenzymes in Epithelial Ovarian Carcinoma: Potential Diagnostic Markers and Therapeutic Targets

Buono¹,

Morone²,

Parrotta³

et al. 2012

Ovarian Cancer - Basic Science Perspective

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Breast cancer cell-associated endopeptidase EC 24.11 modulates proliferative response to bombesin

Cited by 25 publications

References 66 publications

Imbalance between Neutral Endopeptidase 24.11 and Endothelin-1 Expression in Human Endometrial Carcinoma

Imbalance between Neutral Endopeptidase 24.11 and Endothelin-1 Expression in Human Endometrial Carcinoma

Gastrin-Releasing Peptide Is a Growth Factor for Human Neuroblastomas

Ectoenzymes in Epithelial Ovarian Carcinoma: Potential Diagnostic Markers and Therapeutic Targets

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