Abstract | OBJECTIVE: SUMMARY BACKGROUND DATA:
Neuroblastoma 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. METHODS: Sections 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 Ca2+ 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. RESULTS: Immunohistochemical 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 [Ca2+]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. CONCLUSIONS: These 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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Authors | Sunghoon Kim, Wanqin Hu, David R Kelly, Mark R Hellmich, B Mark Evers, Dai H Chung |
Journal | Annals of surgery
(Ann Surg)
Vol. 235
Issue 5
Pg. 621-9; discussion 629-30
(May 2002)
ISSN: 0003-4932 [Print] United States |
PMID | 11981207
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Growth Substances
- RNA, Messenger
- Receptors, Bombesin
- Gastrin-Releasing Peptide
- Calcium
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Topics |
- Calcium
(metabolism)
- Cell Division
- Cell Line
- Child, Preschool
- Gastrin-Releasing Peptide
(metabolism, physiology)
- Growth Substances
(physiology)
- Humans
- Immunohistochemistry
- Infant
- Neuroblastoma
(metabolism)
- RNA, Messenger
(biosynthesis)
- Receptors, Bombesin
(metabolism, physiology)
- Reverse Transcriptase Polymerase Chain Reaction
- Tumor Cells, Cultured
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