Evidence map›Paper›PMID 41185637›Full record

ArticleCellular and molecular bioengineering2025

Strain Promotes Triple Negative Breast Cancer Proliferation and Migration Via VEGFR-2.

Shalarria Cooper, Molly Matthews, Michael Knight, Sharmila Sridhar, Anna Sorace, Lalita A Shevde, M K Sewell-Loftin

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Article in Cellular and molecular bioengineering, 2025. 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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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Shalarria CooperDepartment of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL 35294 USA.
Molly MatthewsDepartment of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL 35294 USA.
Michael KnightHeersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233 USA.
Sharmila SridharDepartment of Radiology, University of Alabama at Birmingham, Birmingham, USA 35233.
Anna SoraceDepartment of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL 35294 USA.
Lalita A ShevdeO'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233 USA.
M K Sewell-LoftinDepartment of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL 35294 USA.ORCID 0000-0003-1985-6899

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Triple negative breast cancer (TNBC) has significantly worse outcomes compared to other subtypes. Strains in the tumor microenvironment (TME) generated by cancer-associated fibroblasts (CAFs) can regulate TNBC progression. Recent studies suggest that expression of VEGFR-2 on TNBC is linked to decreased survival, while our prior studies show strains activate VEGFR-2 to drive angiogenesis. We hypothesized that VEGFR-2 on TNBC can be mechanically activated to alter migration and proliferation. Methods: We utilized MDA-MB-231 TNBC cells loaded into the center chamber of a multi-microtissue TME model; opposing side chambers were loaded with CAFs or normal breast fibroblasts (NBFs). A second series of studies utilized magnetic beads to generate strains in the model without secretion of growth factors. Microtissues were analyzed for TNBC migration and proliferation via Ki67 staining. Results: TNBC cells migrated significantly more towards CAFs compared to NBFs (5×); TME models with magnetic beads showed a 2× increase in migration compared to no strain controls. TNBC cells treated with shRNA against VEGFR-2 demonstrated decreased overall migration but still significantly more towards CAFs vs. NBFs (2×). Proliferation analyses showed strain significantly increased Ki67 in control cells (10%+ vs. 28%+) but not in shVEGFR-2 TNBC (~ 10% all conditions). Discussion: These studies demonstrate that strain in the TME drives increased migration and proliferation of TNBC. Loss of VEGFR-2 suppresses migration and growth, even with mechanical stimulation. Therefore, our results suggest that mechanosignaling via VEGFR-2 on TNBC may regulate disease progression and potentially explain failure of anti-VEGFR-2 drugs in breast cancer patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-025-00866-x.

Indexed as

Microphysiological systemsTriple negative breast cancerTumor mechanobiologyTumor microenvironment

Identifiers

PMID41185637
PMCPMC12579648

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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.