Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 3/2014

01-03-2014 | Original Paper

High expression of metabotropic glutamate receptor 4: correlation with clinicopathologic characteristics and prognosis of osteosarcoma

Authors: Wu Yang, He Maolin, Zhao Jinmin, Wang Zhe

Published in: Journal of Cancer Research and Clinical Oncology | Issue 3/2014

Login to get access

Abstract

Purpose

Analyze protein and gene expression of mGluRs (mGluR1, mGluR5, mGluR4) in osteosarcoma tissues and discuss the relation between expression level and clinical characteristics of osteosarcoma, and study the clinical significance.

Methods

Detect protein and mRNA expression level of mGluRs (mGluR1, mGluR5, mGluR4) in 40 osteosarcoma tissues and the corresponding adjacent normal tissues by Western blot and RT-PCR accordingly. Immunohistochemistry was adopted to detect the expression of mGluRs (mGluR1, mGluR5, mGluR4) in 118 paraffin embedded osteosarcoma tissues and eight normal bone tissues. Then, the correlation between the expression and clinical characteristics of patients was analyzed. Furthermore, survival analysis of osteosarcoma was performed to study the relation between expression level of mGluRs and patient prognosis.

Results

No correlation of mGluR1 and mGluR5 with clinicopathologic characteristics of osteosarcoma was found. Statistical analysis demonstrated that the expression level of mGluR4 shared no significant correlation with gender, age, histologic type and tumor location of patient, but was related to Enneking stage and tumor metastasis (P < 0.05). High mGluR4 expression is more frequently noted in the osteosarcoma tissues with higher Enneking stage and metastasis. The results of Western blot and RT-PCR indicated a significantly increased expression level of mGluR4 gene and protein in osteosarcoma tissues compared with normal tissues. Though higher gene and protein expression of mGluR5 and mGluR1 were also indicated in osteosarcoma tissues compared with normal tissues, no statistical significance was noted for the difference (P > 0.05). According to the survival analysis of 118 osteosarcoma patients, cases in the mGluR4 high-expression group showed inferior disease-free survival rate and poorer overall survival rate.

Conclusion

High expression of mGluR4 in osteosarcoma tissues is related to poor prognosis, thus holding certain reference value for estimating prognosis of osteosarcoma patients.
Literature
go back to reference Aramori I, Nakanishi S (1992) Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor, mGluR1, in transfected CHO cells. Neuron 8:757–765PubMedCrossRef Aramori I, Nakanishi S (1992) Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor, mGluR1, in transfected CHO cells. Neuron 8:757–765PubMedCrossRef
go back to reference Brice NL, Varadi A, Ashcroft SJ et al (2002) Metabotropic glutamate and GABA (B) receptors contribute to the modulation of glucose-stimulated insulin secretion in pancreatic beta cells. Diabetologia 45:242–252PubMedCrossRef Brice NL, Varadi A, Ashcroft SJ et al (2002) Metabotropic glutamate and GABA (B) receptors contribute to the modulation of glucose-stimulated insulin secretion in pancreatic beta cells. Diabetologia 45:242–252PubMedCrossRef
go back to reference Brocke KS, Staufner C, Luksch H et al (2010) Glutamate receptors in pediatric tumors of the central nervous system. Cancer Biol Ther 9:455–468PubMedCrossRef Brocke KS, Staufner C, Luksch H et al (2010) Glutamate receptors in pediatric tumors of the central nervous system. Cancer Biol Ther 9:455–468PubMedCrossRef
go back to reference Carrle D, Bielack S (2009) Osteosarcoma lung metastases detection and principles of multimodal therapy. Cancer Treat Res 152:165–184PubMedCrossRef Carrle D, Bielack S (2009) Osteosarcoma lung metastases detection and principles of multimodal therapy. Cancer Treat Res 152:165–184PubMedCrossRef
go back to reference Chang HJ, Yoo BC, Lim SB et al (2005) Metabotropic glutamate receptor 4 expression in colorectal carcinoma and its prognostic significance. Clin Cancer Res 11:3288–3295PubMedCrossRef Chang HJ, Yoo BC, Lim SB et al (2005) Metabotropic glutamate receptor 4 expression in colorectal carcinoma and its prognostic significance. Clin Cancer Res 11:3288–3295PubMedCrossRef
go back to reference Errani C, Longhi A, Rossi G et al (2011) Palliative therapy for osteosarcoma. Expert Rev Anticancer Ther 11:217–227PubMedCrossRef Errani C, Longhi A, Rossi G et al (2011) Palliative therapy for osteosarcoma. Expert Rev Anticancer Ther 11:217–227PubMedCrossRef
go back to reference Genever PG, Maxfield SJ, Kennovin GD et al (1999) Evidence for a novel glutamate-mediated signaling pathway in keratinocytes. J Invest Dermatol 112:337–342PubMedCrossRef Genever PG, Maxfield SJ, Kennovin GD et al (1999) Evidence for a novel glutamate-mediated signaling pathway in keratinocytes. J Invest Dermatol 112:337–342PubMedCrossRef
go back to reference Gill J, Ahluwalia MK, Geller D et al (2013) New targets and approaches in osteosarcoma. Pharmacol Ther 137:89–99PubMedCrossRef Gill J, Ahluwalia MK, Geller D et al (2013) New targets and approaches in osteosarcoma. Pharmacol Ther 137:89–99PubMedCrossRef
go back to reference Griffin KJ, Kirschner LS, Matyakhina L et al (2004) A transgenic mouse bearing an antisense construct of regulatory subunit type 1A of protein kinase a develops endocrine and other tumours: comparison with Carney Complex and other PRKAR1A induced lesions. J Med Genet 41:923–931PubMedCrossRef Griffin KJ, Kirschner LS, Matyakhina L et al (2004) A transgenic mouse bearing an antisense construct of regulatory subunit type 1A of protein kinase a develops endocrine and other tumours: comparison with Carney Complex and other PRKAR1A induced lesions. J Med Genet 41:923–931PubMedCrossRef
go back to reference Harting MT, Blakely ML (2006) Management of osteosarcoma pulmonary metastases. Semin Pediatr Surg 15:25–29PubMedCrossRef Harting MT, Blakely ML (2006) Management of osteosarcoma pulmonary metastases. Semin Pediatr Surg 15:25–29PubMedCrossRef
go back to reference Iacovelli L, Bruno V, Salvatore L et al (2002) Native group-III metabotropic glutamate receptors are coupled to the mitogen-activated protein kinase/phosphatidylinositol-3-kinase pathways. J Neurochem 82:216–223PubMedCrossRef Iacovelli L, Bruno V, Salvatore L et al (2002) Native group-III metabotropic glutamate receptors are coupled to the mitogen-activated protein kinase/phosphatidylinositol-3-kinase pathways. J Neurochem 82:216–223PubMedCrossRef
go back to reference Kalariti N, Lembessis P, Koutsilieris M (2004) Characterization of the glutametergic system in MG-63 osteoblast-like osteosarcoma cells. Anticancer Res 24:3923–3929PubMed Kalariti N, Lembessis P, Koutsilieris M (2004) Characterization of the glutametergic system in MG-63 osteoblast-like osteosarcoma cells. Anticancer Res 24:3923–3929PubMed
go back to reference Marinissen MJ, Gutkind JS (2001) G-protein-coupled receptors and signaling networks: emerging paradigms. Trends Pharmacol Sci 22:368–376PubMedCrossRef Marinissen MJ, Gutkind JS (2001) G-protein-coupled receptors and signaling networks: emerging paradigms. Trends Pharmacol Sci 22:368–376PubMedCrossRef
go back to reference Molyneux SD, Di Grappa MA, Beristain AG et al (2010) Prkar1a is an osteosarcoma tumor suppressor that defines a molecular subclass in mice. J Clin Invest 120:3310–3325PubMedCentralPubMedCrossRef Molyneux SD, Di Grappa MA, Beristain AG et al (2010) Prkar1a is an osteosarcoma tumor suppressor that defines a molecular subclass in mice. J Clin Invest 120:3310–3325PubMedCentralPubMedCrossRef
go back to reference Park SY, Lee SA, Han IH et al (2007) Clinical significance of metabotropic glutamate receptor 5 expression in oral squamous cell carcinoma. Oncol Rep 17:81–87PubMed Park SY, Lee SA, Han IH et al (2007) Clinical significance of metabotropic glutamate receptor 5 expression in oral squamous cell carcinoma. Oncol Rep 17:81–87PubMed
go back to reference Patton AJ, Genever PG, Birch MA et al (1998) Expression of an N-methyl-D-aspartate-type receptor by human and rat osteoblasts and osteoclasts suggests a novel glutamate signaling pathway in bone. Bone 22:645–649PubMedCrossRef Patton AJ, Genever PG, Birch MA et al (1998) Expression of an N-methyl-D-aspartate-type receptor by human and rat osteoblasts and osteoclasts suggests a novel glutamate signaling pathway in bone. Bone 22:645–649PubMedCrossRef
go back to reference Peavy RD, Chang MS, Sanders-Bush E et al (2001) Metabotropic glutamate receptor 5-induced phosphorylation of extracellular signal-regulated kinase in astrocytes depends on transactivation of the epidermal growth factor receptor. J Neurosci 21:9619–9628PubMed Peavy RD, Chang MS, Sanders-Bush E et al (2001) Metabotropic glutamate receptor 5-induced phosphorylation of extracellular signal-regulated kinase in astrocytes depends on transactivation of the epidermal growth factor receptor. J Neurosci 21:9619–9628PubMed
go back to reference Pollock PM, Cohen-Solal K, Sood R et al (2003) Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia. Nat Genet 34:108–112PubMedCrossRef Pollock PM, Cohen-Solal K, Sood R et al (2003) Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia. Nat Genet 34:108–112PubMedCrossRef
go back to reference Seidlitz EP, Sharma MK, Saikali Z et al (2009) Cancer cell lines release glutamate into the extracellular environment. Clin Exp Metastasis 26:781–787PubMedCrossRef Seidlitz EP, Sharma MK, Saikali Z et al (2009) Cancer cell lines release glutamate into the extracellular environment. Clin Exp Metastasis 26:781–787PubMedCrossRef
go back to reference Seidlitz EP, Sharma MK, Singh G (2010) Extracellular glutamate alters mature osteoclast and osteoblast functions. Can J Physiol Pharmacol 88:929–936PubMedCrossRef Seidlitz EP, Sharma MK, Singh G (2010) Extracellular glutamate alters mature osteoclast and osteoblast functions. Can J Physiol Pharmacol 88:929–936PubMedCrossRef
go back to reference Sharma MK, Seidlitz EP, Singh G (2010) Cancer cells release glutamate via the cystine/glutamate antiporter. Biochem Biophys Res Commun 391:91–95PubMedCrossRef Sharma MK, Seidlitz EP, Singh G (2010) Cancer cells release glutamate via the cystine/glutamate antiporter. Biochem Biophys Res Commun 391:91–95PubMedCrossRef
go back to reference Skerry TM (2008) The role of glutamate in the regulation of bone mass and architecture. J Musculoskelet Neuronal Interact 8:166–173PubMed Skerry TM (2008) The role of glutamate in the regulation of bone mass and architecture. J Musculoskelet Neuronal Interact 8:166–173PubMed
go back to reference Skerry TM, Genever PG (2001) Glutamate signalling in non-neuronal tissues. Trends Pharmacol Sci 22:174–181PubMed Skerry TM, Genever PG (2001) Glutamate signalling in non-neuronal tissues. Trends Pharmacol Sci 22:174–181PubMed
go back to reference Stepulak A, Luksch H, Gebhardt C et al (2009) Expression of glutamate receptor subunits in human cancers. Histochem Cell Biol 132:435–445PubMed Stepulak A, Luksch H, Gebhardt C et al (2009) Expression of glutamate receptor subunits in human cancers. Histochem Cell Biol 132:435–445PubMed
go back to reference Takano T, Lin JH, Arcuino G et al (2001) Glutamate release promotes growth of malignant gliomas. Nat Med 7:1010–1015PubMed Takano T, Lin JH, Arcuino G et al (2001) Glutamate release promotes growth of malignant gliomas. Nat Med 7:1010–1015PubMed
go back to reference Tanabe Y, Masu M, Ishii T et al (1992) A family of metabotropic glutamate receptors. Neuron 8:169–179PubMed Tanabe Y, Masu M, Ishii T et al (1992) A family of metabotropic glutamate receptors. Neuron 8:169–179PubMed
go back to reference Thandi S, Blank JL, Challiss RA (2002) Group-I metabotropic glutamate receptors, mGlu1a and mGlu5a, couple to extracellular signal-regulated kinase (ERK) activation via distinct, but overlapping, signalling pathways. J Neurochem 83:1139–1153PubMed Thandi S, Blank JL, Challiss RA (2002) Group-I metabotropic glutamate receptors, mGlu1a and mGlu5a, couple to extracellular signal-regulated kinase (ERK) activation via distinct, but overlapping, signalling pathways. J Neurochem 83:1139–1153PubMed
go back to reference Traynelis SF, Wollmuth LP, McBain CJ et al (2010) Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev 62:405–496PubMed Traynelis SF, Wollmuth LP, McBain CJ et al (2010) Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev 62:405–496PubMed
Metadata
Title
High expression of metabotropic glutamate receptor 4: correlation with clinicopathologic characteristics and prognosis of osteosarcoma
Authors
Wu Yang
He Maolin
Zhao Jinmin
Wang Zhe
Publication date
01-03-2014
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 3/2014
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-013-1581-3

Other articles of this Issue 3/2014

Journal of Cancer Research and Clinical Oncology 3/2014 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.