Evidence map›Paper›PMID 19323811›Full record

ArticleBMC cancer2009

Staged stromal extracellular 3D matrices differentially regulate breast cancer cell responses through PI3K and beta1-integrins.

Remedios Castelló-Cros, David R Khan, Jeffrey Simons, Matthildi Valianou, Edna Cukierman

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

57 citing papers in PubMed, 109 citations in OpenAlex.

  1. Unlocking the Therapeutic Potential of Integrin-Linked Kinase Inhibitors in Bioengineered 3D Breast Tumor Stroma Models.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  9. PersonalizedFrontiers in bioengineering and biotechnology · 2022
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  19. Decellularized Extracellular Matrix for Cancer Research.Materials (Basel, Switzerland) · 2019
    Review
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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 at 2 institutions in 1 country.

Remedios Castelló-CrosCancer Genetics and Signaling Program, Fox Chase Cancer Center, Philadelphia, PA 19111-2497, USA. Remedios.CastelloCros@fccc.edu
David R Khan
Jeffrey Simons
Matthildi Valianou
Edna Cukierman
Fox Chase Cancer Center · USCancer Genetics (United States) · US

Funding

WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Margaret von Mehren · 1985 to 2026
$138.8M
TRAINING PROGRAM IN CANCER RESEARCHT32CA009035 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI CHERNOFF, JONATHAN · 1985 to 2020
$10.5M
3D-Adhesion Stromagenesis in Cancer PermissivenessR01CA113451 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI CUKIERMAN, EDNA · 2006 to 2016
$2.8M
NCI NIH HHS CA-06927NCI NIH HHS P30 CA006927NCI NIH HHS R01 CA113451NCI NIH HHS T32 CA009035
6 · The paper itself

Abstract

backgroundInteractions between cancer cells and stroma are critical for growth and invasiveness of epithelial tumors. The biochemical mechanisms behind tumor-stromal interactions leading to increased invasiveness and metastasis are mostly unknown. The goal of this study was to analyze the direct effects of staged stroma-derived extracellular matrices on breast cancer cell behavior.

methodsEarly and late three-dimensional matrices were produced by NIH-3T3 and tumor-associated murine fibroblasts, respectively. After removing fibroblasts, extracted matrices were re-cultured with breast epithelial cells of assorted characteristics: MCF-10A (non-tumorigenic), MCF-7 (tumorigenic, non-invasive), and MDA-MB-231 (tumorigenic, invasive). Effects prompted by staged matrices on epithelial cell's growth, morphology and invasion were determined. Also, matrix-induced velocity, directionality and relative track orientation of invasive cells were assessed in the presence or absence of inhibitors of phosphoinositide-3 kinase (PI3K) and/or beta-1 integrin.

resultsWe observed that assorted breast epithelial cells reacted differently to two-dimensional vs. staged, control (early) and tumor-associated (late), three-dimensional matrices. MCF-10A had a proliferative advantage on two-dimensional substrates while MCF-7 and MDA-MB-231 showed no difference. MCF-10A and MCF-7 formed morphologically distinguishable aggregates within three-dimensional matrices, while MDA-MB-231 exhibited increased spindle-shape morphologies and directional movements within three-dimensional matrices. Furthermore, MDA-MB-231 acquired a pattern of parallel oriented organization within tumor-associated, but not control matrices. Moreover, tumor-associated matrices induced PI3K and beta1-integrin dependent Akt/PKB activity in MDA-MB-231 cells. Interestingly, beta1-integrin (but not PI3K) regulated tumor-associated matrix-induced mesenchymal invasion which, when inhibited, resulted in a change of invasive strategy rather than impeding invasion altogether.

conclusionWe propose that both cells and matrices are important to promote effective breast cancer cell invasion through three-dimensional matrices and that beta1-integrin inhibition is not necessarily sufficient to block tumor-matrix induced breast cancer cell invasion. Additionally, we believe that characterizing stroma staging (e.g., early vs. late or tumor-associated) might be beneficial for predicting matrix-induced cancer cell responses in order to facilitate the selection of therapies.

Indexed as

AnimalsAntibodies, MonoclonalBreast NeoplasmsCell LineCell Line, TumorCell MovementCell ProliferationCell ShapeCoculture TechniquesEpithelial CellsExtracellular MatrixHumansIntegrin beta1MiceNIH 3T3 CellsPhosphatidylinositol 3-KinasesAntibodies, MonoclonalIntegrin beta1Phosphatidylinositol 3-KinasesProto-Oncogene Proteins c-akt

Identifiers

PMID19323811
PMCPMC2669806
OpenAlexW2014392784

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.