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Published in: Acta Neuropathologica Communications 1/2023

Open Access 01-12-2023 | Pituitary Adenoma | Research

Identification and gene expression profiling of human gonadotrophic pituitary adenoma stem cells

Authors: Linhao Yuan, Peiliang Li, Jiang Li, Jiayi Peng, Jianlong Zhouwen, Shunchang Ma, Guijun Jia, Wang Jia, Peng Kang

Published in: Acta Neuropathologica Communications | Issue 1/2023

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Abstract

Background

Gonadotrophic pituitary adenoma is a major subtype of pituitary adenoma in the sellar region, but it is rarely involved in the hypersecretion of hormones into blood; thus, it is commonly regarded as “non-functioning.” Its tumorigenic mechanisms remain unknown. The aim of this study was to identify human gonadotrophic pituitary adenoma stem cells (hPASCs) and explore the underlying gene expression profiles. In addition, the potential candidate genes involved in the invasive properties of pituitary adenoma were examined.

Methods

The hPASCs from 14 human gonadotrophic pituitary adenoma clinical samples were cultured and verified via immunohistochemistry. Genetic profiling of hPASCs and the matched tumor cells was performed through RNA-sequencing and subjected to enrichment analysis. By aligning the results with public databases, the candidate genes were screened and examined in invasive and non-invasive gonadotrophic pituitary adenomas using Real-time polymerase chain reaction.

Results

The hPASCs were successfully isolated and cultured from gonadotrophic pituitary adenoma in vitro, which were identified as positive for generic stem cell markers (Sox2, Oct4, Nestin and CD133) via immunohistochemical staining. The hPASCs could differentiate into the tumor cells expressing follicle-stimulating hormone in the presence of fetal bovine serum in the culture medium. Through RNA-sequencing, 1352 differentially expressed genes were screened and identified significantly enriched in various gene ontologies and important pathways. The expression levels of ANXA2, PMAIP1, SPRY2, C2CD4A, APOD, FGF14 and FKBP10 were significantly upregulated while FNDC5 and MAP3K4 were downregulated in the invasive gonadotrophic pituitary adenomas compared to the non-invasive ones.

Conclusion

Genetic profiling of hPASCs may explain the tumorigenesis and invasiveness of gonadotrophic pituitary adenoma. ANXA2 may serve as a potential therapeutic target for the treatment of gonadotrophic pituitary adenoma.
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Literature
1.
go back to reference Sivakumar W, Chamoun R, Nguyen V, Couldwell WT (2011) Incidental pituitary adenomas. Neurosurg Focus 31:E18CrossRef Sivakumar W, Chamoun R, Nguyen V, Couldwell WT (2011) Incidental pituitary adenomas. Neurosurg Focus 31:E18CrossRef
2.
go back to reference Neou M, Villa C, Armignacco R, Jouinot A, Raffin-Sanson ML, Septier A et al (2020) Pangenomic classification of pituitary neuroendocrine tumors. Cancer Cell 37:123-134.e5CrossRef Neou M, Villa C, Armignacco R, Jouinot A, Raffin-Sanson ML, Septier A et al (2020) Pangenomic classification of pituitary neuroendocrine tumors. Cancer Cell 37:123-134.e5CrossRef
3.
go back to reference Drummond J, Roncaroli F, Grossman AB, Korbonits M (2019) Clinical and pathological aspects of silent pituitary adenomas. J Clin Endocrinol Metab 104:2473–2489CrossRef Drummond J, Roncaroli F, Grossman AB, Korbonits M (2019) Clinical and pathological aspects of silent pituitary adenomas. J Clin Endocrinol Metab 104:2473–2489CrossRef
4.
go back to reference Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737CrossRef Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737CrossRef
5.
go back to reference Wang JC (2010) Good cells gone bad: the cellular origins of cancer. Trends Mol Med 16:145–151CrossRef Wang JC (2010) Good cells gone bad: the cellular origins of cancer. Trends Mol Med 16:145–151CrossRef
6.
go back to reference Abbaszadegan MR, Bagheri V, Razavi MS, Momtazi AA, Sahebkar A, Gholamin M (2017) Isolation, identification, and characterization of cancer stem cells: a review. J Cell Physiol 232:2008–2018CrossRef Abbaszadegan MR, Bagheri V, Razavi MS, Momtazi AA, Sahebkar A, Gholamin M (2017) Isolation, identification, and characterization of cancer stem cells: a review. J Cell Physiol 232:2008–2018CrossRef
7.
go back to reference Abdullah LN, Chow EK-H (2013) Mechanisms of chemoresistance in cancer stem cells. Clin Transl Med 2:3CrossRef Abdullah LN, Chow EK-H (2013) Mechanisms of chemoresistance in cancer stem cells. Clin Transl Med 2:3CrossRef
8.
go back to reference Zhang S, Cui Y, Ma X, Yong J, Yan L, Yang M et al (2020) Single-cell transcriptomics identifies divergent developmental lineage trajectories during human pituitary development. Nat Commun 11:5275CrossRef Zhang S, Cui Y, Ma X, Yong J, Yan L, Yang M et al (2020) Single-cell transcriptomics identifies divergent developmental lineage trajectories during human pituitary development. Nat Commun 11:5275CrossRef
9.
go back to reference Andoniadou CL, Matsushima D, Mousavy Gharavy SN, Signore M, Mackintosh AI, Schaeffer M et al (2013) Sox2(+) stem/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential. Cell Stem Cell 13:433–445CrossRef Andoniadou CL, Matsushima D, Mousavy Gharavy SN, Signore M, Mackintosh AI, Schaeffer M et al (2013) Sox2(+) stem/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential. Cell Stem Cell 13:433–445CrossRef
10.
go back to reference Xu Q, Yuan X, Tunici P, Liu G, Fan X, Xu M et al (2009) Isolation of tumour stem-like cells from benign tumours. Br J Cancer 101:303–311CrossRef Xu Q, Yuan X, Tunici P, Liu G, Fan X, Xu M et al (2009) Isolation of tumour stem-like cells from benign tumours. Br J Cancer 101:303–311CrossRef
11.
go back to reference Wurth R, Barbieri F, Pattarozzi A, Gaudenzi G, Gatto F, Fiaschi P et al (2017) Phenotypical and pharmacological characterization of stem-like cells in human pituitary adenomas. Mol Neurobiol 54:4879–4895CrossRef Wurth R, Barbieri F, Pattarozzi A, Gaudenzi G, Gatto F, Fiaschi P et al (2017) Phenotypical and pharmacological characterization of stem-like cells in human pituitary adenomas. Mol Neurobiol 54:4879–4895CrossRef
12.
go back to reference Würth R, Thellung S, Corsaro A, Barbieri F, Florio T (2020) Experimental evidence and clinical implications of pituitary adenoma stem cells. Front Endocrinol (Lausanne) 11:54CrossRef Würth R, Thellung S, Corsaro A, Barbieri F, Florio T (2020) Experimental evidence and clinical implications of pituitary adenoma stem cells. Front Endocrinol (Lausanne) 11:54CrossRef
14.
go back to reference Michaelis KA, Knox AJ, Xu M, Kiseljak-Vassiliades K, Edwards MG, Geraci M et al (2011) Identification of growth arrest and DNA-damage-inducible gene beta (GADD45beta) as a novel tumor suppressor in pituitary gonadotrope tumors. Endocrinology 152:3603–3613CrossRef Michaelis KA, Knox AJ, Xu M, Kiseljak-Vassiliades K, Edwards MG, Geraci M et al (2011) Identification of growth arrest and DNA-damage-inducible gene beta (GADD45beta) as a novel tumor suppressor in pituitary gonadotrope tumors. Endocrinology 152:3603–3613CrossRef
15.
go back to reference Newey PJ, Nesbit MA, Rimmer AJ, Head RA, Gorvin CM, Attar M et al (2013) Whole-exome sequencing studies of nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 98:E796-800CrossRef Newey PJ, Nesbit MA, Rimmer AJ, Head RA, Gorvin CM, Attar M et al (2013) Whole-exome sequencing studies of nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 98:E796-800CrossRef
16.
go back to reference Pease M, Ling C, Mack WJ, Wang K, Zada G (2013) The role of epigenetic modification in tumorigenesis and progression of pituitary adenomas: a systematic review of the literature. PLoS ONE 8:e82619CrossRef Pease M, Ling C, Mack WJ, Wang K, Zada G (2013) The role of epigenetic modification in tumorigenesis and progression of pituitary adenomas: a systematic review of the literature. PLoS ONE 8:e82619CrossRef
17.
go back to reference Kober P, Boresowicz J, Rusetska N, Maksymowicz M, Goryca K, Kunicki J et al (2018) DNA methylation profiling in nonfunctioning pituitary adenomas. Mol Cell Endocrinol 473:194–204CrossRef Kober P, Boresowicz J, Rusetska N, Maksymowicz M, Goryca K, Kunicki J et al (2018) DNA methylation profiling in nonfunctioning pituitary adenomas. Mol Cell Endocrinol 473:194–204CrossRef
18.
go back to reference Cheng S, Xie W, Miao Y, Guo J, Wang J, Li C et al (2019) Identification of key genes in invasive clinically non-functioning pituitary adenoma by integrating analysis of DNA methylation and mRNA expression profiles. J Transl Med 17:407CrossRef Cheng S, Xie W, Miao Y, Guo J, Wang J, Li C et al (2019) Identification of key genes in invasive clinically non-functioning pituitary adenoma by integrating analysis of DNA methylation and mRNA expression profiles. J Transl Med 17:407CrossRef
19.
go back to reference Mertens F, Gremeaux L, Chen J, Fu Q, Willems C, Roose H et al (2015) Pituitary tumors contain a side population with tumor stem cell-associated characteristics. Endocr Relat Cancer 22:481–504CrossRef Mertens F, Gremeaux L, Chen J, Fu Q, Willems C, Roose H et al (2015) Pituitary tumors contain a side population with tumor stem cell-associated characteristics. Endocr Relat Cancer 22:481–504CrossRef
20.
go back to reference Peverelli E, Giardino E, Treppiedi D, Meregalli M, Belicchi M, Vaira V et al (2017) Dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists are effective in inhibiting proliferation of progenitor/stem-like cells isolated from nonfunctioning pituitary tumors. Int J Canc J Int du Cancer 140:1870–1880CrossRef Peverelli E, Giardino E, Treppiedi D, Meregalli M, Belicchi M, Vaira V et al (2017) Dopamine receptor type 2 (DRD2) and somatostatin receptor type 2 (SSTR2) agonists are effective in inhibiting proliferation of progenitor/stem-like cells isolated from nonfunctioning pituitary tumors. Int J Canc J Int du Cancer 140:1870–1880CrossRef
21.
go back to reference Capatina C, Cimpean AM, Raica M, Coculescu M, Poiana C (2019) SOX 2 expression in human pituitary adenomas-correlations with pituitary function. In vivo (Athens, Greece) 33:79–83 Capatina C, Cimpean AM, Raica M, Coculescu M, Poiana C (2019) SOX 2 expression in human pituitary adenomas-correlations with pituitary function. In vivo (Athens, Greece) 33:79–83
22.
go back to reference Yunoue S, Arita K, Kawano H, Uchida H, Tokimura H, Hirano H (2011) Identification of CD133+ cells in pituitary adenomas. Neuroendocrinology 94:302–312CrossRef Yunoue S, Arita K, Kawano H, Uchida H, Tokimura H, Hirano H (2011) Identification of CD133+ cells in pituitary adenomas. Neuroendocrinology 94:302–312CrossRef
23.
go back to reference Chen L, Ye H, Wang X, Tang X, Mao Y, Zhao Y et al (2014) Evidence of brain tumor stem progenitor-like cells with low proliferative capacity in human benign pituitary adenoma. Cancer Lett 349:61–66CrossRef Chen L, Ye H, Wang X, Tang X, Mao Y, Zhao Y et al (2014) Evidence of brain tumor stem progenitor-like cells with low proliferative capacity in human benign pituitary adenoma. Cancer Lett 349:61–66CrossRef
24.
go back to reference Orciani M, Davis S, Appolloni G, Lazzarini R, Mattioli-Belmonte M, Ricciuti RA et al (2015) Isolation and characterization of progenitor mesenchymal cells in human pituitary tumors. Cancer Gene Ther 22:9–16CrossRef Orciani M, Davis S, Appolloni G, Lazzarini R, Mattioli-Belmonte M, Ricciuti RA et al (2015) Isolation and characterization of progenitor mesenchymal cells in human pituitary tumors. Cancer Gene Ther 22:9–16CrossRef
25.
go back to reference Koyama-Nasu R, Nasu-Nishimura Y, Todo T, Ino Y, Saito N, Aburatani H et al (2013) The critical role of cyclin D2 in cell cycle progression and tumorigenicity of glioblastoma stem cells. Oncogene 32:3840–3845CrossRef Koyama-Nasu R, Nasu-Nishimura Y, Todo T, Ino Y, Saito N, Aburatani H et al (2013) The critical role of cyclin D2 in cell cycle progression and tumorigenicity of glioblastoma stem cells. Oncogene 32:3840–3845CrossRef
26.
go back to reference Peculis R, Mandrika I, Petrovska R, Dortane R, Megnis K, Nazarovs J et al (2020) Pituispheres contain genetic variants characteristic to pituitary adenoma tumor tissue. Front Endocrinol 11:313CrossRef Peculis R, Mandrika I, Petrovska R, Dortane R, Megnis K, Nazarovs J et al (2020) Pituispheres contain genetic variants characteristic to pituitary adenoma tumor tissue. Front Endocrinol 11:313CrossRef
27.
go back to reference Mitra SK, Hanson DA, Schlaepfer DD (2005) Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol 6:56–68CrossRef Mitra SK, Hanson DA, Schlaepfer DD (2005) Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol 6:56–68CrossRef
28.
go back to reference Cakir M, Grossman AB (2009) Targeting MAPK (Ras/ERK) and PI3K/Akt pathways in pituitary tumorigenesis. Expert Opin Ther Targets 13:1121–1134CrossRef Cakir M, Grossman AB (2009) Targeting MAPK (Ras/ERK) and PI3K/Akt pathways in pituitary tumorigenesis. Expert Opin Ther Targets 13:1121–1134CrossRef
29.
go back to reference Lytle NK, Barber AG, Reya T (2018) Stem cell fate in cancer growth, progression and therapy resistance. Nat Rev Cancer 18:669–680CrossRef Lytle NK, Barber AG, Reya T (2018) Stem cell fate in cancer growth, progression and therapy resistance. Nat Rev Cancer 18:669–680CrossRef
30.
go back to reference Shen X, Liu Q, Xu J, Wang Y (2021) Correlation between the expression of interleukin-6, STAT3, e-cadherin and n-cadherin protein and invasiveness in nonfunctional pituitary adenomas. J Neurol Surg B Skull Base 82:e59-69CrossRef Shen X, Liu Q, Xu J, Wang Y (2021) Correlation between the expression of interleukin-6, STAT3, e-cadherin and n-cadherin protein and invasiveness in nonfunctional pituitary adenomas. J Neurol Surg B Skull Base 82:e59-69CrossRef
31.
go back to reference Mussunoor S, Murray GI (2008) The role of annexins in tumour development and progression. J Pathol 216:131–140CrossRef Mussunoor S, Murray GI (2008) The role of annexins in tumour development and progression. J Pathol 216:131–140CrossRef
32.
go back to reference Sharma MC (2019) Annexin A2 (ANX A2): an emerging biomarker and potential therapeutic target for aggressive cancers. Int J Canc J Int du Canc 144:2074–2081CrossRef Sharma MC (2019) Annexin A2 (ANX A2): an emerging biomarker and potential therapeutic target for aggressive cancers. Int J Canc J Int du Canc 144:2074–2081CrossRef
Metadata
Title
Identification and gene expression profiling of human gonadotrophic pituitary adenoma stem cells
Authors
Linhao Yuan
Peiliang Li
Jiang Li
Jiayi Peng
Jianlong Zhouwen
Shunchang Ma
Guijun Jia
Wang Jia
Peng Kang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Acta Neuropathologica Communications / Issue 1/2023
Electronic ISSN: 2051-5960
DOI
https://doi.org/10.1186/s40478-023-01517-w

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