Evidence map›Paper›PMID 31101720›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2019

A human organoid system that self-organizes to recapitulate growth and differentiation of a benign mammary tumor.

Stefan Florian, Yoshiko Iwamoto, Margaret Coughlin, Ralph Weissleder, Timothy J Mitchison

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
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

15 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Stefan FlorianDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115; stefan.florian@charite.de timothy_mitchison@hms.harvard.edu.
Yoshiko IwamotoCenter for Systems Biology, Richard B. Simches Research Center, Massachusetts General Hospital, Boston, MA 02114.
Margaret CoughlinDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115.
Ralph WeisslederDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115.ORCID 0000-0003-0828-4143
Timothy J MitchisonDepartment of Systems Biology, Harvard Medical School, Boston, MA 02115; stefan.florian@charite.de timothy_mitchison@hms.harvard.edu.

Funding

Quantitative Analysis of Cell Death Pathways in CancerP01CA139980 · NCI · HARVARD MEDICAL SCHOOL · PI WEISSLEDER, MD, PHD, RALPH · 2010 to 2014
$9.0M
Cell and Chemical Biology of MicrotubulesR35GM131753 · NIGMS · HARVARD MEDICAL SCHOOL · PI Timothy J Mitchison · 2019 to 2026
$6.4M
Quantitative analysis of pharmacological mechanism by intravital imagingR01CA164448 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI WEISSLEDER, MD, PHD, RALPH · 2011 to 2015
$4.0M
NCI NIH HHS P01 CA139980NCI NIH HHS R01 CA164448NIGMS NIH HHS R35 GM131753
6 · The paper itself

Abstract

As 3D culture has become central to investigation of tissue biology, mammary epithelial organoids have emerged as powerful tools for investigation of epithelial cell polarization and carcinogenesis. However, most current protocols start from single cells suspended in Matrigel, which can also restrict cell differentiation and behavior. Here, we show that the noncancerous mammary cell line HMT-3522 S1, when allowed to spontaneously form cell aggregates ("spheroids") in medium without Matrigel, switches to a collective growth mode that recapitulates many attributes of "usual ductal hyperplasia" (UDH), a common benign mammary lesion. Interestingly, these spheroids undergo a complex maturation process reminiscent of embryonic development: solid-cell cords form their own basement membrane, grow on the surface of initially homogeneous cell aggregates, and form asymmetric lumina lined by two distinct cell types that express basal and luminal cytokeratins. This sequence of events provides a cellular mechanism that explains how the characteristic crescent-shaped, asymmetrical lumina form in UDH. Our results suggest that HMT-3522 S1 spheroids are useful as an in vitro model system to study UDH biology, glandular lumen formation, and stem cell biology of the mammary gland.

Indexed as

Basement MembraneBreast NeoplasmsCell DifferentiationCell Line, TumorCell ProliferationEpithelial CellsFemaleHumansMammary Glands, HumanOrganoidsepithelial tubelumen formationmammary glandorganoidsusual ductal hyperplasia

Identifiers

PMID31101720
PMCPMC6561274

What OpenQuestion holds

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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.