Evidence map›Paper›PMID 41706033›Full record

ArticleCancer research communications2026

3D "Emboli" Culture Models Epithelial Breast Cancer Cell Oxidative Mitochondrial Metabolism with Relevance for Lung Metastasis.

Kuppusamy Balamurugan, Melissa R Mikolaj, Jonathan M Weiss, Ronald J Holewinski, Yu Fan, Shiba Prasad Dash, Xia Xu, Lois McKennett, Christopher W Dell, Duncan Donohue and 9 more

Abstract read
In one paragraph

Article in Cancer research communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Kuppusamy BalamuruganLaboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, Frederick, Maryland.ORCID 0000-0002-6010-080X
Melissa R MikolajCCR Volume Electron Microscopy (CVEM), Center for Cancer Research, National Cancer Institute, Frederick, Maryland.ORCID 0000-0002-5452-1683
Jonathan M WeissCancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland.ORCID 0000-0002-4467-5611
Ronald J HolewinskiProtein Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.ORCID 0000-0002-3337-3984
Yu FanComputational Genomics and Bioinformatics Branch, Center for Biomedical Informatics and Information Technology, National Cancer Institute, National Institutes of Health, Rockville, Maryland.ORCID 0000-0002-7473-6104
Shiba Prasad DashLaboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, Frederick, Maryland.ORCID 0000-0003-3388-0561
Xia XuProtein Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.ORCID 0000-0002-5449-5067
Lois McKennettLaboratory Animal Sciences Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.ORCID 0009-0003-5035-339X
Christopher W DellCCR Volume Electron Microscopy (CVEM), Center for Cancer Research, National Cancer Institute, Frederick, Maryland.ORCID 0009-0009-2642-5393
Duncan DonohueStatistical Consulting and Scientific Programming Group, Computer and Statistical Services, Data Management Services, Inc (a BRMI Company), National Cancer Institute, Frederick, Maryland.ORCID 0000-0002-3137-8773
Ariana VitaleLaboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, Frederick, Maryland.ORCID 0000-0002-4919-6134
Shashikala RatnayakeComputational Genomics and Bioinformatics Branch, Center for Biomedical Informatics and Information Technology, National Cancer Institute, National Institutes of Health, Rockville, Maryland.ORCID 0009-0005-3660-4070
Shikha SharanLaboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, Frederick, Maryland.ORCID 0000-0001-5885-7304
Qingrong ChenComputational Genomics and Bioinformatics Branch, Center for Biomedical Informatics and Information Technology, National Cancer Institute, National Institutes of Health, Rockville, Maryland.ORCID 0000-0003-1325-6147
Daoud MeerzamanComputational Genomics and Bioinformatics Branch, Center for Biomedical Informatics and Information Technology, National Cancer Institute, National Institutes of Health, Rockville, Maryland.ORCID 0000-0002-0129-5256
Thorkell AndressonProtein Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.ORCID 0000-0002-9545-2450
Daniel W McVicarCancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland.ORCID 0000-0002-1112-5111
Kedar NarayanCCR Volume Electron Microscopy (CVEM), Center for Cancer Research, National Cancer Institute, Frederick, Maryland.ORCID 0000-0001-7982-6494
Esta SterneckLaboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, Frederick, Maryland.ORCID 0000-0001-7716-8766

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
Molecular Mechanisms Regulating Mouse Mammary Gland and Human Breast Tumor CellsZIABC010307 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI STERNECK, GISELA · 2009 to 2025
$22.1M
Intramural NIH HHS ZIA BC010307National Cancer Institute (NCI)NIH HHS 75N91019D00024
6 · The paper itself

Abstract

Three-dimensional (3D) cell culture systems have emerged as powerful tools for modeling tumor biology in ex vivo settings. However, the diverse array of available 3D culture methods presents challenges in selecting the most appropriate model for specific research questions. This study provides a comparative analysis of breast cancer cells (SUM149, IBC-3, and MDA-MB-468) in the mammosphere culture (SphC) model or an "emboli" culture (EmC) model, which enrich for cancer stem cells and epithelial features, respectively. The EmC model, designed originally for inflammatory breast cancer, is characterized by media viscosity and mechanical rocking of the culture vessel. Notably, cells in EmC showed a distinct and durable reduction in cell proliferation ex vivo while demonstrating high capacity to establish experimental lung metastases in vivo. Ultrastructural quantitative analysis of electron microscopy images suggested that cells in EmC acquire nuclear and mitochondrial features that resemble those of tumor tissue. Proteomics, single-cell transcriptomics, and metabolic flux analyses showed that cells in EmC and SphC favor mitochondrial oxidative metabolism (OXPHOS) and glycolysis, respectively. EmC rendered cells hypersensitive to OXPHOS inhibition but more resistant to oxidative stress. Several genes associated with lung metastasis, including ID1, were specifically enriched in EmC. Given the emerging role of OXPHOS in breast cancer cell survival during dissemination and as established metastases, we propose that the EmC paradigm is a suitable ex vivo model to study signaling pathways relevant for basal epithelial breast cancer, including lung metastases, and to assess drug sensitivities and resistance mechanisms of such breast cancer cells ex vivo. SIGNIFICANCE: This study provides an in-depth characterization of a resource-efficient, yet powerful 3D culture paradigm to improve the physiologic relevance of ex vivo approaches. Applicable to epithelial cancers, this model offers a platform to accelerate the discovery of physiologically relevant signaling pathways and specific cancer cell vulnerabilities.

Indexed as

Breast NeoplasmsCell Culture Techniques, Three DimensionalLung NeoplasmsMitochondriaAnimalsCell Line, TumorCell ProliferationFemaleHumansMetabolic ReprogrammingMiceNeoplastic Stem Cells

Identifiers

PMID41706033
PMCPMC13012061

What OpenQuestion holds

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Registered trials

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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.