Evidence map›Paper›PMID 28077158›Full record

ArticleBreast cancer research : BCR2017

CCL2-driven inflammation increases mammary gland stromal density and cancer susceptibility in a transgenic mouse model.

Xuan Sun, Danielle J Glynn, Leigh J Hodson, Cecilia Huo, Kara Britt, Erik W Thompson, Lucy Woolford, Andreas Evdokiou, Jeffrey W Pollard, Sarah A Robertson and 1 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Breast cancer research : BCR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04170335 (Effects of Bariatric Surgery on Breast Density Improvement and Its Impact on Breast Cancer Risk in Morbidly Obese Patients), which is not on this map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
3.4field-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.

NCT04170335 withdrawnnot on this mapstarted 2021, after this paper: background citation

Effects of Bariatric Surgery on Breast Density Improvement and Its Impact on Breast Cancer Risk in Morbidly Obese Patients

TypeobservationalSponsorThe Cleveland ClinicRan2021 to 2023Enrolled0ConditionsBreast Cancer, Morbid Obesity, Bariatric Surgery CandidateArmsBariatric surgery
3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.

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  11. Targeting CCL2/CCR2 Signaling Overcomes MEK Inhibitor Resistance in Acute Myeloid Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
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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

11 authors at 6 institutions in 2 countries.

Xuan SunDiscipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, Adelaide, Australia.
Danielle J GlynnDiscipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, Adelaide, Australia.
Leigh J HodsonThe Robinson Research Institute, University of Adelaide, Adelaide, Australia.
Cecilia HuoThe University of Melbourne Department of Surgery, St Vincent's Hospital Melbourne, Fitzroy, Australia.
Kara BrittMetastasis Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia.
Erik W ThompsonThe University of Melbourne Department of Surgery, St Vincent's Hospital Melbourne, Fitzroy, Australia.
Lucy WoolfordSchool of Veterinary Sciences, University of Adelaide, Roseworthy, SA, Australia.
Andreas EvdokiouDiscipline of Surgery, School of Medicine, The Queen Elizabeth Hospital, University of Adelaide, DX465702, 28 Woodville Rd, Woodville, 5011, Australia.
Jeffrey W PollardMRC and University of Edinburgh Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Sarah A RobertsonDiscipline of Obstetrics and Gynaecology, School of Medicine, University of Adelaide, Adelaide, Australia.
Wendy V IngmanThe Robinson Research Institute, University of Adelaide, Adelaide, Australia. wendy.ingman@adelaide.edu.au.
University of Adelaide · AUQueen Elizabeth Hospital · AUMRC Centre for Reproductive Health · GBPeter MacCallum Cancer Centre · AUQueensland University of Technology · AUUniversity of Melbourne · AU

Funding

Tumor Progression and MetastasisP01CA100324 · NCI · YESHIVA UNIVERSITY · PI CONDEELIS, JOHN S · 2003 to 2018
$30.0M
The Metastatic Cascade: Macrophages Lead the WayR01CA172451 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI POLLARD, JEFFREY W. · 2013 to 2017
$2.2M
Medical Research Council G1002033Medical Research Council MR/N022556/1NCI NIH HHS P01 CA100324NCI NIH HHS R01 CA172451Wellcome TrustWellcome Trust 101067/Z/13/Z
6 · The paper itself

Abstract

backgroundMacrophages play diverse roles in mammary gland development and breast cancer. CC-chemokine ligand 2 (CCL2) is an inflammatory cytokine that recruits macrophages to sites of injury. Although CCL2 has been detected in human and mouse mammary epithelium, its role in regulating mammary gland development and cancer risk has not been explored.

methodsTransgenic mice were generated wherein CCL2 is driven by the mammary epithelial cell-specific mouse mammary tumour virus 206 (MMTV) promoter. Estrous cycles were tracked in adult transgenic and non-transgenic FVB mice, and mammary glands collected at the four different stages of the cycle. Dissected mammary glands were assessed for cyclical morphological changes, proliferation and apoptosis of epithelium, macrophage abundance and collagen deposition, and mRNA encoding matrix remodelling enzymes. Another cohort of control and transgenic mice received carcinogen 7,12-Dimethylbenz(a)anthracene (DMBA) and tumour development was monitored weekly. CCL2 protein was also quantified in paired samples of human breast tissue with high and low mammographic density.

resultsOverexpression of CCL2 in the mammary epithelium resulted in an increased number of macrophages, increased density of stroma and collagen and elevated mRNA encoding matrix remodelling enzymes lysyl oxidase (LOX) and tissue inhibitor of matrix metalloproteinases (TIMP)3 compared to non-transgenic controls. Transgenic mice also exhibited increased susceptibility to development of DMBA-induced mammary tumours. In a paired sample cohort of human breast tissue, abundance of epithelial-cell-associated CCL2 was higher in breast tissue of high mammographic density compared to tissue of low mammographic density.

conclusionsConstitutive expression of CCL2 by the mouse mammary epithelium induces a state of low level chronic inflammation that increases stromal density and elevates cancer risk. We propose that CCL2-driven inflammation contributes to the increased risk of breast cancer observed in women with high mammographic density.

Indexed as

Disease SusceptibilityAnimalsBreast DensityBreast NeoplasmsChemokine CCL2Chemotaxis, LeukocyteDisease Models, AnimalEpitheliumEstrous CycleFemaleGene ExpressionHumansInflammationKaplan-Meier EstimateMacrophagesMammary Glands, HumanChemokine CCL2RNA, MessengerChemokine (C-C motif) ligand 2DevelopmentMacrophageMammary glandMammographic densityMouse model

Identifiers

PMID28077158
PMCPMC5225654
OpenAlexW2579860480

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.