Evidence map›Paper›PMID 24204192›Full record

ArticleNeoplasia (New York, N.Y.)2013

Acid-mediated tumor proteolysis: contribution of cysteine cathepsins.

Jennifer M Rothberg, Kate M Bailey, Jonathan W Wojtkowiak, Yael Ben-Nun, Matthew Bogyo, Ekkehard Weber, Kamiar Moin, Galia Blum, Raymond R Mattingly, Robert J Gillies and 1 more

Open access · goldAbstract read
In one paragraph

Article in Neoplasia (New York, N.Y.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 6% 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

61 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.

  1. Pooled it
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  12. Metastatic triple negative breast cancer adapts its metabolism to destination tissues while retaining key metabolic signatures.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
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  14. Cancer heterogeneity and metastasis: life at the edge.Clinical & experimental metastasis · 2022
    Review
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1 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

11 authors at 5 institutions in 3 countries.

Jennifer M RothbergCancer Biology Program, Wayne State University, Detroit, MI ; Department of Pharmacology, Wayne State University, Detroit, MI.
Kate M Bailey
Jonathan W Wojtkowiak
Yael Ben-Nun
Matthew Bogyo
Ekkehard Weber
Kamiar Moin
Galia Blum
Raymond R Mattingly
Robert J Gillies
Bonnie F Sloane
Wayne State University · USMoffitt Cancer Center · USHebrew University of Jerusalem · ILMartin Luther University Halle-Wittenberg · DEStanford University · US

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI Christine O'Connell · 1998 to 2026
$93.5M
Tumor Biology and Microenvironment (Program 1)P30CA022453 · NCI · WAYNE STATE UNIVERSITY · PI Julie Lynn Boerner · 1985 to 2026
$68.4M
The Physi(ologi)cal Microenvironment and its Role in Tumor Invasion and MetastaseU54CA143970 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI GATENBY, ROBERT A · 2009 to 2014
$9.3M
Causes & Consequences of Acid pH in TumorsR01CA077575 · NCI · UNIVERSITY OF ARIZONA · PI GILLIES, ROBERT J. · 1999 to 2018
$8.5M
Proteolytic Pathways in Progression of Pre-Malignant Breast DiseaseR01CA131990 · NCI · WAYNE STATE UNIVERSITY · PI MATTINGLY, RAYMOND R, SLOANE, BONNIE F · 2008 to 2013
$1.9M
NCI NIH HHS P30 CA022453NCI NIH HHS P30 CA076292NCI NIH HHS P30 CA22453NCI NIH HHS R01 CA077575NCI NIH HHS R01 CA131990NCI NIH HHS U54 CA143970
6 · The paper itself

Abstract

One of the noncellular microenvironmental factors that contribute to malignancy of solid tumors is acidic peritumoral pH. We have previously demonstrated that extracellular acidosis leads to localization of the cysteine pro-tease cathepsin B on the tumor cell membrane and its secretion. The objective of the present study was to determine if an acidic extracellular pH such as that observed in vivo (i.e., pHe 6.8) affects the activity of proteases, e.g., cathepsin B, that contribute to degradation of collagen IV by tumor cells when grown in biologically relevant three-dimensional (3D) cultures. For these studies, we used 1) 3D reconstituted basement membrane overlay cultures of human carcinomas, 2) live cell imaging assays to assess proteolysis, and 3) in vivo imaging of active tumor proteases. At pHe 6.8, there were increases in pericellular active cysteine cathepsins and in degradation of dye-quenched collagen IV, which was partially blocked by a cathepsin B inhibitor. Imaging probes for active cysteine cathepsins localized to tumors in vivo. The amount of bound probe decreased in tumors in bicarbonate-treated mice, a treatment previously shown to increase peritumoral pHe and reduce local invasion of the tumors. Our results are consistent with the acid-mediated invasion hypothesis and with a role for cathepsin B in promoting degradation of a basement membrane protein substrate, i.e., type IV collagen, in an acidic peritumoral environment.

Indexed as

AnimalsBreast NeoplasmsCathepsin BCell Line, TumorCollagen Type IVColonic NeoplasmsEnzyme PrecursorsExtracellular FluidFemaleHeterograftsHumansHydrogen-Ion ConcentrationMiceMice, SCIDNeoplasm TransplantationProteolysisCathepsin BCollagen Type IVEnzyme Precursors

Identifiers

PMID24204192
PMCPMC3819629
OpenAlexW1926273606

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.