Evidence map›Paper›PMID 21613822›Full record

ArticleCancer biology & therapy2011

A novel 3-dimensional culture system uncovers growth stimulatory actions by TGFβ in pancreatic cancer cells.

Lorenzo F Sempere, Jason R Gunn, Murray Korc

Open access · hybridAbstract read
In one paragraph

Article in Cancer biology & therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

34 citing papers in PubMed, 54 citations in OpenAlex.

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  5. Engineering of biomaterials for tumor modeling.Materials today. Advances · 2020
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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

3 authors at 1 institution in 1 country.

Lorenzo F SempereDepartment of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA. Lorenzo.F.Sempere@Dartmouth.edu
Jason R Gunn
Murray Korc
Dartmouth–Hitchcock Medical Center · US

Funding

Novel aspects of Epithelial-Mesenchymal Transition(EMT)in pancreatic cancerR01CA075059 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI KORC, MURRAY · 1997 to 2018
$4.3M
Dysregulation of TGF Beta Action Pancreatic CancerR37CA075059 · NCI · INDIANA UNIVERSITY INDIANAPOLIS · PI KORC, MURRAY · 2008 to 2012
$2.2M
NCI NIH HHS CA-R37-075059NCI NIH HHS R01 CA075059
6 · The paper itself

Abstract

Transforming Growth Factor-β (TGF-β) exerts cell type-specific and context-dependent effects. Understanding the intrinsic effects of TGF-β on cancer cells in pancreatic ductal adenocarcinoma (PDAC) is a prerequisite for rationalized clinical implementation of TGF-β targeting therapies. Since the tumor microenvironment can affect how cancer cell respond to TGF-β, we employed a novel three-dimensional (3D) culturing system to recapitulate stromal and extracellular matrix interactions. We show here that TGF-β stimulates growth of human and murine pancreatic cancer cell lines (PCCs) when embedded in a 3% collagen IV/laminin-rich gelatinous medium (Matrigel™) over a solidified layer of soft agar. Moreover, in this novel 3D model, concomitant treatment with TGF-β1 and epidermal growth factor (EGF) enhanced PCC growth to a greater extent than either growth factor alone, and conferred increased chemoresistance to cytotoxic compounds. These cooperative growth-stimulatory effects were blocked by pharmacological inhibition of TGF-β type I receptor with SB431542 or the EGF receptor with erlotinib. Co-incubation with SB431542 and erlotinib enhanced the efficacy of gemcitabine and cisplatin in PCCs and in primary cell cultures established from pancreata of genetically-engineered mouse models of PDAC. These findings suggest that concomitant inhibition of TGF-β and EGF signaling may represent an effective therapeutic strategy in PDAC, and that this 3D culturing system could be utilized to test ex vivo the therapeutic response of pancreatic tumor biopsies from PDAC patients, thereby providing a functional assay to facilitate personalized targeted therapies.

Indexed as

AnimalsBenzamidesCarcinoma, Pancreatic DuctalCell Culture TechniquesCell Line, TumorCell ProliferationCisplatinCulture MediaDeoxycytidineDioxolesDrug Resistance, NeoplasmEpidermal Growth FactorErbB ReceptorsErlotinib HydrochlorideExtracellular MatrixGemcitabine4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideBenzamidesCisplatinCulture MediaDeoxycytidineDioxolesEpidermal Growth FactorErbB ReceptorsErlotinib HydrochlorideGemcitabineQuinazolinesReceptors, Transforming Growth Factor betaTransforming Growth Factor betaTransforming Growth Factor beta1

Identifiers

PMID21613822
PMCPMC3166497
OpenAlexW2065247841

What OpenQuestion holds

Textmetadata
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.