Evidence map›Paper›PMID 33773184›Full record

ArticleEBioMedicine2021

A human ACTH-secreting corticotroph tumoroid model: Novel Human ACTH-Secreting Tumor Cell in vitro Model.

Dongyun Zhang, Willy Hugo, Peter Redublo, Hui Miao, Marvin Bergsneider, Marilene B Wang, Won Kim, William H Yong, Anthony P Heaney

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.6field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
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  8. scRNA sequencing technology for PitNET studies.Frontiers in endocrinology · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Dongyun ZhangDepartments of Medicine, David Geffen School of Medicine, University of California, Los Angeles, United States.
Willy HugoDepartments of Medicine, David Geffen School of Medicine, University of California, Los Angeles, United States.
Peter RedubloDepartments of Medicine, David Geffen School of Medicine, University of California, Los Angeles, United States.
Hui MiaoDepartments of Medicine, David Geffen School of Medicine, University of California, Los Angeles, United States.
Marvin BergsneiderDepartments of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, United States.
Marilene B WangDepartments of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, United States.
Won KimDepartments of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, United States.
William H YongDepartments of Pathology and Lab Medicine, David Geffen School of Medicine, University of California, Los Angeles, United States.
Anthony P HeaneyDepartments of Medicine, David Geffen School of Medicine, University of California, Los Angeles, United States; Departments of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, United States. Electronic address: aheaney@mednet.ucla.edu.
University of California, Los Angeles · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
Development of 3-dimensional human pituitary corticotroph tumor cultures as a preclinical model for drug discoveryR01CA251930 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HEANEY, ANTHONY P · 2021 to 2025
$1.8M
NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA211015NCI NIH HHS R01 CA251930
6 · The paper itself

Abstract

backgroundCushing disease (CD), although rare, is a life-threatening disorder caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma, which leads to excess adrenal-derived cortisol. Efficacious and safe medical therapies that control both hormonal hypersecretion and pituitary corticotroph tumor growth remain an unmet need in the management of CD. Translational research in pituitary tumors has been significantly hampered by limited quantities of surgically resected tissue for ex vivo studies, and unavailability of human pituitary tumor cell models.

methodsTo characterize human corticotroph tumors at the cellular level, we employed single cell RNA-sequencing (scRNA-seq) to study 4 surgically resected tumors. We also used microarrays to compare individualized paired consecutive culture passages to understand transcriptional shifts as in vitro cultures lost ACTH secretion. Based on these findings, we then modified our in vitro culture methods to develop sustained ACTH-secreting human corticotroph tumoroid cultures.

findingsscRNA-seq identified 4 major cell populations, namely corticotroph tumor (73.6%), stromal (11.2%), progenitor (8.3%), and immune cells (6.8%). Microarray analysis revealed striking changes in extracellular matrix, cell adhesion and motility-related genes concordant with loss of ACTH secretion during conventional 2D culture. Based on these findings, we subsequently defined a series of crucial culture nutrients and scaffold modifications that provided a more favorable trophic and structural environment that could maintain ACTH secretion in in vitro human corticotroph tumor cultures for up to 4 months.

interpretationOur human corticotroph tumoroid model is a significant advance in the field of pituitary tumors and will further enable translational research studies to identify critically needed therapies for CD.

fundingThis work was partly funded by NCI P50-CA211015 and the Warley Trust Foundation.

Indexed as

ACTH-Secreting Pituitary AdenomaBiomarkersCell Line, TumorCell ProliferationCells, CulturedComputational BiologyGene Expression ProfilingHigh-Throughput Nucleotide SequencingHumansPituitary ACTH HypersecretionSingle-Cell AnalysisSpheroids, CellularTumor Cells, CulturedBiomarkers3D cultureAdrenocorticotropic hormone (ACTH)Cushing disease (CD)Proopiomelanocortin (POMC)

Identifiers

PMID33773184
PMCPMC8024915
OpenAlexW3146716660

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.