Evidence map›Paper›PMID 30234012›Full record

ArticleFrontiers in oncology2018

Phenotypic Basis for Matrix Stiffness-Dependent Chemoresistance of Breast Cancer Cells to Doxorubicin.

M Hunter Joyce, Carolyne Lu, Emily R James, Rachel Hegab, Shane C Allen, Laura J Suggs, Amy Brock

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

Article in Frontiers in oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 1 pooled it
6.6field-weighted citation impact, top 2% 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

73 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.

  1. 3DACS biomaterials science & engineering · 2023
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13 more citing papers are in PubMed but not listed here.

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

7 authors at 2 institutions in 1 country.

M Hunter JoyceDepartment of Biomedical Engineering, University of Texas at Austin, Austin, TX, United States.
Carolyne LuDepartment of Biomedical Engineering, University of Texas at Austin, Austin, TX, United States.
Emily R JamesDepartment of Biomedical Engineering, University of Texas at Austin, Austin, TX, United States.
Rachel HegabDepartment of Biomedical Engineering, Louisiana Tech University, Ruston, LA, United States.
Shane C AllenDepartment of Biomedical Engineering, University of Texas at Austin, Austin, TX, United States.
Laura J SuggsDepartment of Biomedical Engineering, University of Texas at Austin, Austin, TX, United States.
Amy BrockDepartment of Biomedical Engineering, University of Texas at Austin, Austin, TX, United States.
The University of Texas at Austin · USLouisiana Tech University · US

Funding

The Allee Effect in Tumor InitiationR01CA226258 · NCI · UNIVERSITY OF TEXAS AT AUSTIN · PI BROCK, AMY, HUANG, SUI · 2018 to 2022
$2.3M
High resolution cell lineage tracking and isolationR21CA212928 · NCI · UNIVERSITY OF TEXAS AT AUSTIN · PI BROCK, AMY · 2017 to 2019
$559k
NCI NIH HHS R01 CA226258NCI NIH HHS R21 CA212928
6 · The paper itself

Abstract

The persistence of drug resistant cell populations following chemotherapeutic treatment is a significant challenge in the clinical management of cancer. Resistant subpopulations arise via both cell intrinsic and extrinsic mechanisms. Extrinsic factors in the microenvironment, including neighboring cells, glycosaminoglycans, and fibrous proteins impact therapy response. Elevated levels of extracellular fibrous proteins are associated with tumor progression and cause the surrounding tissue to stiffen through changes in structure and composition of the extracellular matrix (ECM). We sought to determine how this progressively stiffening microenvironment affects the sensitivity of breast cancer cells to chemotherapeutic treatment. MDA-MB-231 triple negative breast carcinoma cells cultured in a 3D alginate-based hydrogel system displayed a stiffness-dependent response to the chemotherapeutic doxorubicin. MCF7 breast carcinoma cells cultured in the same conditions did not exhibit this stiffness-dependent resistance to the drug. This differential therapeutic response was coordinated with nuclear translocation of YAP, a marker of mesenchymal differentiation. The stiffness-dependent response was lost when cells were transferred from 3D to monolayer cultures, suggesting that endpoint ECM conditions largely govern the response to doxorubicin. To further examine this response, we utilized a platform capable of dynamic ECM stiffness modulation to allow for a change in matrix stiffness over time. We found that MDA-MB-231 cells have a stiffness-dependent resistance to doxorubicin and that duration of exposure to ECM stiffness is sufficient to modulate this response. These results indicate the need for additional tools to integrate mechanical stiffness with therapeutic response and inform decisions for more effective use of chemotherapeutics in the clinic.

Indexed as

3D cell culturechemotherapyextracellular matrixresistancetumor microenvironment

Identifiers

PMID30234012
PMCPMC6134055
OpenAlexW2890625366

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.