Abstract:
:Pituitary adenomas cause significant endocrine and mass-related morbidity. Little is known about the mechanisms that underlie pituitary tumor pathogenesis. In the present study, we searched for a side population (SP) in pituitary tumors representing cells with high efflux capacity and potentially enriched for tumor stem cells (TSCs). Human pituitary adenomas contain a SP irrespective of hormonal phenotype. This adenoma SP, as well as the purified SP (pSP) that is depleted from endothelial and immune cells, is enriched for cells that express 'tumor stemness' markers and signaling pathways, including epithelial-mesenchymal transition (EMT)-linked factors. Pituitary adenomas were found to contain self-renewing sphere-forming cells, considered to be a property of TSCs. These sphere-initiating cells were recovered in the pSP. Because benign pituitary adenomas do not grow in vitro and have failed to expand in immunodeficient mice, the pituitary tumor cell line AtT20 was further used. We identified a SP in this cell line and found it to be more tumorigenic than the non-SP 'main population'. Of the two EMT regulatory pathways tested, the inhibition of chemokine (C-X-C motif) receptor 4 (CXCR4) signaling reduced EMT-associated cell motility in vitro as well as xenograft tumor growth, whereas the activation of TGFβ had no effect. The human adenoma pSP also showed upregulated expression of the pituitary stem cell marker SOX2. Pituitaries from dopamine receptor D2 knockout (Drd2(-/-)) mice that bear prolactinomas contain more pSP, Sox2(+), and colony-forming cells than WT glands. In conclusion, we detected a SP in pituitary tumors and identified TSC-associated characteristics. The present study adds new elements to the unraveling of pituitary tumor pathogenesis and may lead to the identification of new therapeutic targets.
journal_name
Endocr Relat Cancerjournal_title
Endocrine-related cancerauthors
Mertens F,Gremeaux L,Chen J,Fu Q,Willems C,Roose H,Govaere O,Roskams T,Cristina C,Becú-Villalobos D,Jorissen M,Poorten VV,Bex M,van Loon J,Vankelecom Hdoi
10.1530/ERC-14-0546subject
Has Abstractpub_date
2015-08-01 00:00:00pages
481-504issue
4eissn
1351-0088issn
1479-6821pii
ERC-14-0546journal_volume
22pub_type
杂志文章abstract::Hypoxia occurs in solid tumours due to a mismatch between tumour growth and angiogenesis. Hypoxia in solid tumours is associated with an aggressive phenotype and resistance to radiation therapy and chemotherapy leading to poor patient prognosis. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor, which is ac...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.1.01290
更新日期:2006-12-01 00:00:00
abstract::Carrying excess body fat is a leading cause of cancer. Epidemiologic evidence gives strong clues about the mechanisms that link excess adiposity to risk for several cancer sites. For postmenopausal breast cancer and endometrial cancer, the hyper-estrogenic state that is induced by excess body fatness is the likely cau...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-14-0580
更新日期:2015-06-01 00:00:00
abstract::Deubiquitinases (DUBs) play important roles and therefore are potential drug targets in various diseases including cancer and neurodegeneration. In this review, we recapitulate structure-function studies of the most studied DUBs including USP7, USP22, CYLD, UCHL1, BAP1, A20, as well as ataxin 3 and connect them to reg...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-14-0516
更新日期:2015-02-01 00:00:00
abstract::The thyroid hormones T3 and T4 have emerged as pro-angiogenic hormones with important implications for cancer management. Endogenous circulating hormone levels may help stimulate cancer progression and limit the effectiveness of anticancer therapy, though clinical data remain inconclusive. The capacity of thyroid horm...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-19-0058
更新日期:2019-06-01 00:00:00
abstract::Quantitative reverse transcription-polymerase chain reaction (RT-PCR) used to detect minor changes in specific mRNA concentrations may be associated with poor reproducibility. Stringent quality control is therefore essential at each step of the protocol, including the PCR procedure. We performed inter-laboratory quali...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.00808
更新日期:2004-09-01 00:00:00
abstract::Metabolic disorders such as diabetes, obesity and the metabolic syndrome have been shown to modulate prostate cancer (PCa) risk and aggressiveness in population-based and experimental studies. While associations between these conditions are modest and complex, two consistent findings have emerged. First, there is obse...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-12-0067
更新日期:2012-09-05 00:00:00
abstract::Medullary thyroid cancer (MTC) is a rare tumor arising from the calcitonin-producing parafollicular C cells of the thyroid gland, occurring either sporadically or alternatively in a hereditary form based on germline RET mutations in approximately one-third of cases. Historically, patients with advanced, metastasized M...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-16-0104
更新日期:2016-06-01 00:00:00
abstract::Combined clinical and laboratory investigations of multiple endocrine neoplasia type 1 (MEN1) have resulted in an increased understanding of this disorder which may be inherited as an autosomal dominant condition. Defining the features of each disease manifestation in MEN1 has improved patient management and treatment...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.0.0060449
更新日期:1999-12-01 00:00:00
abstract::To analyze the genetic alterations of pheochromocytomas and evaluate the difference among malignant, extra-adrenal, and benign pheochromocytomas. Forty-three tumor samples were tested for genetic changes using multiplex ligation-dependent probe amplification. Among them, 39 samples were available for protein expressio...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-07-0188
更新日期:2008-03-01 00:00:00
abstract::Genetic alteration is the driving force for thyroid tumorigenesis and progression, based upon which novel approaches to the management of thyroid cancer can be developed. A recent important genetic finding in thyroid cancer is the oncogenic T1799A transversion mutation of BRAF (the gene for the B-type Raf kinase, BRAF...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.1.0978
更新日期:2005-06-01 00:00:00
abstract::Ghrelin is a hormone with multiple physiologic functions, including promotion of growth hormone release, stimulation of appetite and regulation of energy homeostasis. Treatment with ghrelin/ghrelin-receptor agonists is a prospective therapy for disease-related cachexia and malnutrition. In vitro studies have shown hig...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-16-0130
更新日期:2016-09-01 00:00:00
abstract::Components of the tumour microenvironment initiate and promote cancer development. In this study, we investigated the stromal component of parathyroid neoplasia. Immunohistochemistry for alpha-smooth muscle actin (α-SMA) showed an abundant periacinar distribution of α-SMA(+) cells in normal parathyroid glands (n=3). T...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-14-0161
更新日期:2015-02-01 00:00:00
abstract::ThyroSeq v2 claims high positive (PPV) and negative (NPV) predictive values in a wide range of pretest risks of malignancy in indeterminate thyroid nodules (ITNs) (categories B-III and B-IV of the Bethesda system). We evaluated ThyroSeq v2 performance in a cohort of patients with ITNs seen at our Academic Cancer Cente...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-16-0512
更新日期:2017-03-01 00:00:00
abstract::Non-functioning pituitary adenomas, recently alternatively termed pituitary neuroendocrine tumours (NFpitNETs), are mostly benign neoplasms that are not associated with a hormonal hypersecretory syndrome. The clinical spectrum of NFpitNETs varies from completely asymptomatic to the development of panhypopituitarism an...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-20-0136
更新日期:2020-10-01 00:00:00
abstract::Although targeted therapy, including inhibitors of mammalian target of rapamycin (mTOR) and vascular endothelial growth factor, being developed for carcinoids arised from the gastrointestinal tract, treatment for locally advanced or metastatic bronchial carcinoids (BCs) remains lacking. Traditional cytotoxic chemother...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-10-0290
更新日期:2011-04-28 00:00:00
abstract::This review describes human and rodent-derived cell lines and xenografts developed over the last five decades that are suitable or potentially suitable models for paraganglioma-pheochromocytoma research. We outline the strengths and weaknesses of various models and emphasize the recurring theme that, despite the major...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-19-0434
更新日期:2020-12-01 00:00:00
abstract::Benign adrenal tumors cover a spectrum of lesions with distinct morphology and steroid secretion. Current classification is empirical. Beyond a few driver mutations, pathophysiology is not well understood. Here, a pangenomic characterization of benign adrenocortical tumors is proposed, aiming at unbiased classificatio...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-20-0128
更新日期:2021-01-01 00:00:00
abstract::Pancreatic neuroendocrine neoplasms (PNENs) constitute a rare tumour entity, and prognosis and treatment options depend on tumour-mediating hallmarks such as angiogenesis, proliferation rate and resistance to apoptosis. The molecular pathways that determine the malignant phenotype are still insufficiently understood a...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-14-0152
更新日期:2014-01-01 00:00:00
abstract::This review is focused on mouse models for prostate cancer that have been designed on the basis of genetic alterations that are frequently found in human prostate cancer. It begins with an analysis of the similarities and differences in the gross and microscopic anatomy of the mouse and human prostate glands, and exte...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.0.0110225
更新日期:2004-06-01 00:00:00
abstract::Recent studies have indicated that a high-fat diet (HFD) plays an important role in prostate cancer (PCa) progression. Palmitic acid (PA) is one of the most abundant saturated free fatty acids (FAs) and is associated with carcinogenesis. In this study, we investigated the mechanism underlying the association of dietar...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-13-0227
更新日期:2013-12-16 00:00:00
abstract::Studies of cell models and profiling of clinical breast cancer material to reveal the mechanisms of resistance to anti-oestrogen therapy, and to tamoxifen in particular, have reported that this phenomenon can be associated with increased expression and signalling through erbB Type 1 growth factor receptors, notably th...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.1.01059
更新日期:2005-07-01 00:00:00
abstract::Somatostatin-producing neuroendocrine tumors (SOM-NETs) of the duodenum and pancreas appear to be heterogeneous. To determine their clinicopathological profiles, respective data were analyzed on a series of 82 duodenal and 541 pancreatic NETs. In addition, the clinical records of 821 patients with duodenal or pancreat...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,多中心研究
doi:10.1677/ERC-07-0157
更新日期:2008-03-01 00:00:00
abstract::Medullary thyroid carcinomas (MTC) arise from thyroid parafollicular, calcitonin-producing C-cells and can occur either as sporadic or as hereditary diseases in the context of familial syndromes, including multiple endocrine neoplasia 2A (MEN2A), multiple endocrine neoplasia 2B (MEN2B) and familial MTC (FMTC). In a la...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-17-0303
更新日期:2018-02-01 00:00:00
abstract::Prostate cancer is the most common cancer in men, resulting in over 10 000 deaths/year in the UK. Sequencing and copy number analysis of primary tumours has revealed heterogeneity within tumours and an absence of recurrent founder mutations, consistent with non-genetic disease initiating events. Using methylation prof...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-14-0454
更新日期:2015-04-01 00:00:00
abstract::Epidemiologic and experimental evidence suggest that a subset of breast cancer is insulin responsive, but it is unclear whether safe and effective therapies that target the insulin receptor (IR), which is homologous to oncogenes of the tyrosine kinase class, can be developed. We demonstrate that both pharmacologic inh...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-11-0136
更新日期:2011-11-14 00:00:00
abstract::Metastatic duodenopancreatic neuro-endocrine tumors (dpNETs) are the most important disease-related cause of death in patients with multiple endocrine neoplasia type 1 (MEN1). Nonfunctioning pNETs (NF-pNETs) are highly prevalent in MEN1 and clinically heterogeneous. Therefore, management is controversial. Data on prog...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-19-0372
更新日期:2020-06-01 00:00:00
abstract::Thyroid cancer is the most common cancer of the endocrine system and is responsible for the majority of deaths from endocrine malignancies. Although a large proportion of thyroid cancers belong to well differentiated histologic subtypes, which in general show a good prognosis after surgery and radioiodine ablation, th...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-13-0271
更新日期:2013-12-16 00:00:00
abstract::Neuroendocrine neoplasms (NEN) are a class of tumours heterogeneous in terms of their anatomical sites of origin and clinical behaviour. Outdated perspectives of indolence have been superseded by appreciation for their myriad clinical challenges, such as the high rates of regional and distant metastases at initial dia...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-20-0074
更新日期:2020-09-01 00:00:00
abstract::The Hippo signaling pathway has been implicated as a conserved regulator of organ size in both Drosophila and mammals. Yes-associated protein (YAP), the central component of the Hippo signaling cascade, functions as an oncogene in several malignancies. Ovarian granulosa cell tumors (GCT) are characterized by enlargeme...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-13-0339
更新日期:2014-03-04 00:00:00
abstract::Therapeutic options for patients with metastatic medullary thyroid carcinoma (MTC) are limited due to lack of effective treatments. Thus, there is a need to thoroughly characterize the pathways of molecular pathogenesis and to identify potential targets for therapy in MTC. Since epidermal growth factor receptor (EGFR)...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-08-0304
更新日期:2010-01-29 00:00:00