Evidence map›Paper›PMID 42234219›Full record

ArticleClinical & experimental metastasis2026

Modeling the role of urokinase-type plasminogen activator, uPA, and circulating cancer-associated fibroblasts (cCAFs) in breast cancer cell extravasation.

Angela Spartz, Susan Schmidt, Fazila Mohamed, Benjamin Troness, Carol A Lange, Dorraya El-Ashry

Abstract read
In one paragraph

Article in Clinical & experimental metastasis, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Angela SpartzMasonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA.
Susan SchmidtMasonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA.
Fazila MohamedMasonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA.
Benjamin TronessUniversity of Texas Health San Antonio, San Antonio, TX, 78229, USA.
Carol A LangeMasonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA. lange047@umn.edu.
Dorraya El-AshryDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, 55455, USA. delashry@bcrf.org.

Funding

Progesterone Receptor (PR) Signaling Cross Talk Drives ER+ Breast CancerR01CA229697 · NCI · UNIVERSITY OF MINNESOTA · PI Carol A Lange, Douglas Yee · 2020 to 2026
$3.6M
Breast Cancer Research Foundation 00086668NIH HHS R01 CA229697U.S. Department of Defense W81XWH-19-1-0699
6 · The paper itself

Abstract

Circulating Cancer-Associated Fibroblasts (cCAFs) have been identified in circulating tumor cell clusters from all stages of disease progression in breast cancer patients. We have shown that CAFs promote lung metastases in the mouse tail vein model when they are clustered with triple negative breast cancer (TNBC) MDA-MB231 cells. Following on this observation, we saw that MDA-MB231-luciferase labeled cells persist at higher levels when present in CAF23/MDA-MB231 co-clusters compared to MDA-MB231 mono-clusters within the first 3 days after tail vein injection. This prompted us to investigate whether CAFs aid cancer cell extravasation from capillary venules into the lung parenchyma, which would impart better survival and faster seeding of metastases. Ex vivo lung extravasation assays showed that within the first 8-24 h after tail vein injection, more cells from CAF23/MDA-MB231 co-clusters extravasated than cells from MDA-MB231 mono-clusters. Using in vitro endothelial binding assays, we determined that CAF/TNBC co-clusters bind to HUVEC endothelial cells better than TNBC mono-clusters. Single-Cell RNA sequencing identified several genes in the fibrinolysis pathway whose expression increases in TNBC cells when they are clustered with CAFs. One of these genes is PLAU, which encodes the urokinase-type plasminogen activator, uPA. siRNA knockdown of PLAU decreased in vitro TNBC-endothelial cell interactions and ex vivo extravasation of MDA-MB231 mono-clusters, revealing a potential role for CAF-induced factors expressed in TNBC cells, such as uPA/PLAU, in breast cancer cell extravasation. Our data helps to define the role of CAFs in breast cancer extravasation and highlights the importance of our previous work showing that CAFs promote tumor cell dissemination and metastasis.

Indexed as

Breast NeoplasmsCancer-Associated FibroblastsLung NeoplasmsNeoplastic Cells, CirculatingTriple Negative Breast NeoplasmsUrokinase-Type Plasminogen ActivatorAnimalsCell Line, TumorFemaleHumansMDA-MB-231 CellsMembrane ProteinsMiceMembrane ProteinsPLAU protein, humanUrokinase-Type Plasminogen ActivatorBreast cancerCancer-associated fibroblastsCirculating tumor cell clustersExtravasationMetastasisUrokinase-type plasminogen activator

Identifiers

PMID42234219
PMCPMC13233632

What OpenQuestion holds

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LicenceCC BY
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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.