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Published in: Journal of Translational Medicine 1/2019

Open Access 01-12-2019 | Meningioma | Research

The clinical characteristics and molecular mechanism of pituitary adenoma associated with meningioma

Authors: Haibo Zhu, Yazhou Miao, Yutao Shen, Jing Guo, Weiyan Xie, Sida Zhao, Wei Dong, Yazhuo Zhang, Chuzhong Li

Published in: Journal of Translational Medicine | Issue 1/2019

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Abstract

Background

Pituitary adenoma and meningioma are the most common benign tumors in the central nervous system. Pituitary adenoma associated with meningioma (PAM) is a rare disease and the clinical features and mechanisms of PAM are unclear.

Methods

We summarized the clinical data of 57 PAM patients and compared with sporadic pituitary adenoma (SPA) and sporadic meningioma (SM). 5 pituitary adenomas of PAM and 5 SPAs were performed ceRNA microarray. qRT-PCR, Western Blot, siMEN1 and rapamycin inhibition experiment were validated for ceRNA microarray.

Results

Clinical variable analyses revealed that significant correlations between PAM and female sex as well as older age when compared with SPA and significant correlations between PAM and transitional meningioma as well as older age when compared with SM. Additionally, the characteristics of PAM were significantly different for MEN1 patients. Functional experiments showed lower expression of MEN1 can upregulate mTOR signaling, in accordance with the result of ceRNA microarray. Rapamycin treatment promotes apoptosis in primary pituitary adenoma and meningioma cells of PAM.

Conclusions

MEN1 plays an important role in PAM by upregulating mTOR signaling pathway. Rapamycin represents a potential therapeutic strategy for PAM in the future.
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Literature
1.
go back to reference McDowell BD, Wallace RB, Carnahan RM, Chrischilles EA, Lynch CF, Schlechte JA. Demographic differences in incidence for pituitary adenoma. Pituitary. 2011;14:23–30.CrossRef McDowell BD, Wallace RB, Carnahan RM, Chrischilles EA, Lynch CF, Schlechte JA. Demographic differences in incidence for pituitary adenoma. Pituitary. 2011;14:23–30.CrossRef
2.
go back to reference Lecoq AL, Kamenicky P, Guiochon-Mantel A, Chanson P. Genetic mutations in sporadic pituitary adenomas–what to screen for? Nat Rev Endocrinol. 2015;11:43–54.CrossRef Lecoq AL, Kamenicky P, Guiochon-Mantel A, Chanson P. Genetic mutations in sporadic pituitary adenomas–what to screen for? Nat Rev Endocrinol. 2015;11:43–54.CrossRef
3.
go back to reference Amirjamshidi A, Mortazavi SA, Shirani M, Saeedinia S, Hanif H. Coexisting pituitary adenoma and suprasellar meningioma-a coincidence or causation effect: report of two cases and review of the literature. J Surg Case Rep. 2017;2017:rjx039.CrossRef Amirjamshidi A, Mortazavi SA, Shirani M, Saeedinia S, Hanif H. Coexisting pituitary adenoma and suprasellar meningioma-a coincidence or causation effect: report of two cases and review of the literature. J Surg Case Rep. 2017;2017:rjx039.CrossRef
4.
go back to reference Ruiz-Juretschke F, Iza B, Scola-Pliego E, Poletti D, Salinero E. Coincidental pituitary adenoma and planum sphenoidale meningioma mimicking a single tumor. Endocrinol Nutr. 2015;62:292–4.CrossRef Ruiz-Juretschke F, Iza B, Scola-Pliego E, Poletti D, Salinero E. Coincidental pituitary adenoma and planum sphenoidale meningioma mimicking a single tumor. Endocrinol Nutr. 2015;62:292–4.CrossRef
5.
go back to reference Bondy M, Ligon BL. Epidemiology and etiology of intracranial meningiomas: a review. J Neurooncol. 1996;29:197–205.CrossRef Bondy M, Ligon BL. Epidemiology and etiology of intracranial meningiomas: a review. J Neurooncol. 1996;29:197–205.CrossRef
6.
go back to reference Curto L, Squadrito S, Almoto B, Longo M, Granata F, Salpietro F, Torre ML, Marini F, Trimarchi F, Cannavo S. MRI finding of simultaneous coexistence of growth hormone-secreting pituitary adenoma with intracranial meningioma and carotid artery aneurysms: report of a case. Pituitary. 2007;10:299–305.CrossRef Curto L, Squadrito S, Almoto B, Longo M, Granata F, Salpietro F, Torre ML, Marini F, Trimarchi F, Cannavo S. MRI finding of simultaneous coexistence of growth hormone-secreting pituitary adenoma with intracranial meningioma and carotid artery aneurysms: report of a case. Pituitary. 2007;10:299–305.CrossRef
7.
go back to reference Herrero-Ruiz A, Villanueva-Alvarado HS, Corrales-Hernandez JJ, Higueruela-Minguez C, Feito-Perez J, Recio-Cordova JM. Coexistence of GH-producing pituitary macroadenoma and meningioma in a patient with multiple endocrine neoplasia type 1 with hyperglycemia and ketosis as first clinical sign. Case Rep Endocrinol. 2017;2017:2390797.PubMedPubMedCentral Herrero-Ruiz A, Villanueva-Alvarado HS, Corrales-Hernandez JJ, Higueruela-Minguez C, Feito-Perez J, Recio-Cordova JM. Coexistence of GH-producing pituitary macroadenoma and meningioma in a patient with multiple endocrine neoplasia type 1 with hyperglycemia and ketosis as first clinical sign. Case Rep Endocrinol. 2017;2017:2390797.PubMedPubMedCentral
8.
go back to reference Concolino P, Costella A, Capoluongo E. Multiple endocrine neoplasia type 1 (MEN1): an update of 208 new germline variants reported in the last nine years. Cancer Genet. 2016;209:36–41.CrossRef Concolino P, Costella A, Capoluongo E. Multiple endocrine neoplasia type 1 (MEN1): an update of 208 new germline variants reported in the last nine years. Cancer Genet. 2016;209:36–41.CrossRef
9.
go back to reference Agarwal SK. The future: genetics advances in MEN1 therapeutic approaches and management strategies. Endocr Relat Cancer. 2017;24:T119–34.CrossRef Agarwal SK. The future: genetics advances in MEN1 therapeutic approaches and management strategies. Endocr Relat Cancer. 2017;24:T119–34.CrossRef
10.
go back to reference Weber F, Mulligan LM. Happy 20th anniversary MEN1: from positional cloning to gene function restoration. Endocr Relat Cancer. 2017;24:E7–11.CrossRef Weber F, Mulligan LM. Happy 20th anniversary MEN1: from positional cloning to gene function restoration. Endocr Relat Cancer. 2017;24:E7–11.CrossRef
11.
go back to reference Asgharian B, Chen YJ, Patronas NJ, Peghini PL, Reynolds JC, Vortmeyer A, Zhuang Z, Venzon DJ, Gibril F, Jensen RT. Meningiomas may be a component tumor of multiple endocrine neoplasia type 1. Clin Cancer Res. 2004;10:869–80.CrossRef Asgharian B, Chen YJ, Patronas NJ, Peghini PL, Reynolds JC, Vortmeyer A, Zhuang Z, Venzon DJ, Gibril F, Jensen RT. Meningiomas may be a component tumor of multiple endocrine neoplasia type 1. Clin Cancer Res. 2004;10:869–80.CrossRef
12.
go back to reference Wu YJ, Wong BS, Yea SH, Lu CI, Weng SH. Sinularin induces apoptosis through mitochondria dysfunction and inactivation of the pI3K/Akt/mTOR pathway in gastric carcinoma cells. Mar Drugs. 2016;14:E142.CrossRef Wu YJ, Wong BS, Yea SH, Lu CI, Weng SH. Sinularin induces apoptosis through mitochondria dysfunction and inactivation of the pI3K/Akt/mTOR pathway in gastric carcinoma cells. Mar Drugs. 2016;14:E142.CrossRef
13.
go back to reference Chen S, Fisher RC, Signs S, Molina LA, Shenoy AK, Lopez MC, Baker HV, Koomen JM, Chen Y, Gittleman H, et al. Inhibition of PI3K/Akt/mTOR signaling in PI3KR2-overexpressing colon cancer stem cells reduces tumor growth due to apoptosis. Oncotarget. 2017;8:50476–88.PubMed Chen S, Fisher RC, Signs S, Molina LA, Shenoy AK, Lopez MC, Baker HV, Koomen JM, Chen Y, Gittleman H, et al. Inhibition of PI3K/Akt/mTOR signaling in PI3KR2-overexpressing colon cancer stem cells reduces tumor growth due to apoptosis. Oncotarget. 2017;8:50476–88.PubMed
14.
go back to reference Pachow D, Wick W, Gutmann DH, Mawrin C. The mTOR signaling pathway as a treatment target for intracranial neoplasms. Neuro Oncol. 2015;17:189–99.CrossRef Pachow D, Wick W, Gutmann DH, Mawrin C. The mTOR signaling pathway as a treatment target for intracranial neoplasms. Neuro Oncol. 2015;17:189–99.CrossRef
15.
go back to reference Li J, Li C, Wang J, Song G, Zhao Z, Wang H, Wang W, Li H, Li Z, Miao Y, et al. Genome-wide analysis of differentially expressed lncRNAs and mRNAs in primary gonadotrophin adenomas by RNA-seq. Oncotarget. 2017;8:4585–606.PubMed Li J, Li C, Wang J, Song G, Zhao Z, Wang H, Wang W, Li H, Li Z, Miao Y, et al. Genome-wide analysis of differentially expressed lncRNAs and mRNAs in primary gonadotrophin adenomas by RNA-seq. Oncotarget. 2017;8:4585–606.PubMed
16.
go back to reference Pachow D, Andrae N, Kliese N, Angenstein F, Stork O, Wilisch-Neumann A, Kirches E, Mawrin C. mTORC1 inhibitors suppress meningioma growth in mouse models. Clin Cancer Res. 2013;19:1180–9.CrossRef Pachow D, Andrae N, Kliese N, Angenstein F, Stork O, Wilisch-Neumann A, Kirches E, Mawrin C. mTORC1 inhibitors suppress meningioma growth in mouse models. Clin Cancer Res. 2013;19:1180–9.CrossRef
17.
go back to reference Surace EI, Lusis E, Haipek CA, Gutmann DH. Functional significance of S6K overexpression in meningioma progression. Ann Neurol. 2004;56:295–8.CrossRef Surace EI, Lusis E, Haipek CA, Gutmann DH. Functional significance of S6K overexpression in meningioma progression. Ann Neurol. 2004;56:295–8.CrossRef
18.
go back to reference James MF, Han S, Polizzano C, Plotkin SR, Manning BD, Stemmer-Rachamimov AO, Gusella JF, Ramesh V. NF2/merlin is a novel negative regulator of mTOR complex 1, and activation of mTORC1 is associated with meningioma and schwannoma growth. Mol Cell Biol. 2009;29:4250–61.CrossRef James MF, Han S, Polizzano C, Plotkin SR, Manning BD, Stemmer-Rachamimov AO, Gusella JF, Ramesh V. NF2/merlin is a novel negative regulator of mTOR complex 1, and activation of mTORC1 is associated with meningioma and schwannoma growth. Mol Cell Biol. 2009;29:4250–61.CrossRef
19.
go back to reference Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev. 2000;21:215–44.CrossRef Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev. 2000;21:215–44.CrossRef
20.
go back to reference O’Neil TK, Duffy LR, Frey JW, Hornberger TA. The role of phosphoinositide 3-kinase and phosphatidic acid in the regulation of mammalian target of rapamycin following eccentric contractions. J Physiol. 2009;587:3691–701.CrossRef O’Neil TK, Duffy LR, Frey JW, Hornberger TA. The role of phosphoinositide 3-kinase and phosphatidic acid in the regulation of mammalian target of rapamycin following eccentric contractions. J Physiol. 2009;587:3691–701.CrossRef
21.
go back to reference Liang J, Slingerland JM. Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression. Cell Cycle. 2003;2:339–45.CrossRef Liang J, Slingerland JM. Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression. Cell Cycle. 2003;2:339–45.CrossRef
22.
go back to reference Mafficini A, Scarpa A. Genomic landscape of pancreatic neuroendocrine tumours: the International Cancer Genome Consortium. J Endocrinol. 2018;236:R161–7.CrossRef Mafficini A, Scarpa A. Genomic landscape of pancreatic neuroendocrine tumours: the International Cancer Genome Consortium. J Endocrinol. 2018;236:R161–7.CrossRef
23.
go back to reference Majumder PK, Febbo PG, Bikoff R, Berger R, Xue Q, McMahon LM, Manola J, Brugarolas J, McDonnell TJ, Golub TR, et al. mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat Med. 2004;10:594–601.CrossRef Majumder PK, Febbo PG, Bikoff R, Berger R, Xue Q, McMahon LM, Manola J, Brugarolas J, McDonnell TJ, Golub TR, et al. mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat Med. 2004;10:594–601.CrossRef
24.
go back to reference Wen PY, Chang SM, Lamborn KR, Kuhn JG, Norden AD, Cloughesy TF, Robins HI, Lieberman FS, Gilbert MR, Mehta MP, et al. Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas: North American Brain Tumor Consortium trial 04-02. Neuro Oncol. 2014;16:567–78.CrossRef Wen PY, Chang SM, Lamborn KR, Kuhn JG, Norden AD, Cloughesy TF, Robins HI, Lieberman FS, Gilbert MR, Mehta MP, et al. Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas: North American Brain Tumor Consortium trial 04-02. Neuro Oncol. 2014;16:567–78.CrossRef
25.
go back to reference Lee EQ, Kuhn J, Lamborn KR, Abrey L, DeAngelis LM, Lieberman F, Robins HI, Chang SM, Yung WK, Drappatz J, et al. Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma: North American Brain Tumor Consortium study 05-02. Neuro Oncol. 2012;14:1511–8.CrossRef Lee EQ, Kuhn J, Lamborn KR, Abrey L, DeAngelis LM, Lieberman F, Robins HI, Chang SM, Yung WK, Drappatz J, et al. Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma: North American Brain Tumor Consortium study 05-02. Neuro Oncol. 2012;14:1511–8.CrossRef
26.
go back to reference Lassen U, Sorensen M, Gaziel TB, Hasselbalch B, Poulsen HS. Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme. Anticancer Res. 2013;33:1657–60.PubMed Lassen U, Sorensen M, Gaziel TB, Hasselbalch B, Poulsen HS. Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme. Anticancer Res. 2013;33:1657–60.PubMed
27.
go back to reference Franz DN, Belousova E, Sparagana S, Bebin EM, Frost M, Kuperman R, Witt O, Kohrman MH, Flamini JR, Wu JY, et al. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2013;381:125–32.CrossRef Franz DN, Belousova E, Sparagana S, Bebin EM, Frost M, Kuperman R, Witt O, Kohrman MH, Flamini JR, Wu JY, et al. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2013;381:125–32.CrossRef
28.
go back to reference Krueger DA, Care MM, Holland K, Agricola K, Tudor C, Mangeshkar P, Wilson KA, Byars A, Sahmoud T, Franz DN. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med. 2010;363:1801–11.CrossRef Krueger DA, Care MM, Holland K, Agricola K, Tudor C, Mangeshkar P, Wilson KA, Byars A, Sahmoud T, Franz DN. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med. 2010;363:1801–11.CrossRef
29.
go back to reference Franz DN, Leonard J, Tudor C, Chuck G, Care M, Sethuraman G, Dinopoulos A, Thomas G, Crone KR. Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol. 2006;59:490–8.CrossRef Franz DN, Leonard J, Tudor C, Chuck G, Care M, Sethuraman G, Dinopoulos A, Thomas G, Crone KR. Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol. 2006;59:490–8.CrossRef
30.
go back to reference Cerovac V, Monteserin-Garcia J, Rubinfeld H, Buchfelder M, Losa M, Florio T, Paez-Pereda M, Stalla GK, Theodoropoulou M. The somatostatin analogue octreotide confers sensitivity to rapamycin treatment on pituitary tumor cells. Cancer Res. 2010;70:666–74.CrossRef Cerovac V, Monteserin-Garcia J, Rubinfeld H, Buchfelder M, Losa M, Florio T, Paez-Pereda M, Stalla GK, Theodoropoulou M. The somatostatin analogue octreotide confers sensitivity to rapamycin treatment on pituitary tumor cells. Cancer Res. 2010;70:666–74.CrossRef
Metadata
Title
The clinical characteristics and molecular mechanism of pituitary adenoma associated with meningioma
Authors
Haibo Zhu
Yazhou Miao
Yutao Shen
Jing Guo
Weiyan Xie
Sida Zhao
Wei Dong
Yazhuo Zhang
Chuzhong Li
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2019
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-019-2103-0

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