Evidence map›Paper›PMID 34237033›Full record

ArticleJCI insight2021

DDR1-induced neutrophil extracellular traps drive pancreatic cancer metastasis.

Jenying Deng, Yaan Kang, Chien-Chia Cheng, Xinqun Li, Bingbing Dai, Matthew H Katz, Taoyan Men, Michael P Kim, Eugene A Koay, Huocong Huang and 2 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed
12.8field-weighted citation impact, top 1% 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

94 citing papers in PubMed, 153 citations in OpenAlex.

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34 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

12 authors at 4 institutions in 2 countries.

Jenying DengDepartment of Surgical Oncology.
Yaan KangDepartment of Experimental Therapeutics.
Chien-Chia ChengDepartment of Molecular and Cellular Oncology.
Xinqun LiDepartment of Surgical Oncology.
Bingbing DaiDepartment of Surgical Oncology.
Matthew H KatzDepartment of Surgical Oncology.
Taoyan MenDepartment of Surgical Oncology.
Michael P KimDepartment of Surgical Oncology.
Eugene A KoayDepartment of Radiation Oncology.
Huocong HuangDepartment of Surgery and Hamon Center for Therapeutic Oncology Research, Division of Surgical Oncology, and.
Rolf A BrekkenDepartment of Surgery and Hamon Center for Therapeutic Oncology Research, Division of Surgical Oncology, and.
Jason B FlemingDepartment of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
ID Genomics (United States) · USMoffitt Cancer Center · USPediatrics and Genetics · USThe University of Texas Southwestern Medical Center · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5M
Transport Oncophysics CoreU54CA210181 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI WANG, RONGFU · 2016 to 2020
$9.3M
Exploitation of RAS signaling to develop therapy and early detection strategies for PDAR01CA192381 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI BREKKEN, ROLF A, WILKIE, THOMAS M · 2015 to 2019
$2.2M
Targeted inhibition in stromal TGFβ activity in pancreatic cancerR01CA243577 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI BREKKEN, ROLF A · 2020 to 2023
$1.7M
NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA076292NCI NIH HHS R01 CA192381NCI NIH HHS R01 CA243577NCI NIH HHS U54 CA210181
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) tumors are characterized by a desmoplastic reaction resulting in dense deposition of collagen that is known to promote cancer progression. A central mediator of protumorigenic collagen signaling is the receptor tyrosine kinase discoid domain receptor 1 (DDR1). DDR1 is a critical driver of a mesenchymal and invasive cancer cell PDAC phenotype. Previous studies have demonstrated that genetic or pharmacologic inhibition of DDR1 reduces PDAC tumorigenesis and metastasis. Here, we investigated whether DDR1 signaling has cancer cell nonautonomous effects that promote PDAC progression and metastasis. We demonstrate that collagen-induced DDR1 activation in cancer cells is a major stimulus for CXCL5 production, resulting in the recruitment of tumor-associated neutrophils (TANs), the formation of neutrophil extracellular traps (NETs), and subsequent cancer cell invasion and metastasis. Moreover, we have identified that collagen-induced CXCL5 production was mediated by a DDR1/PKCθ/SYK/NF-κB signaling cascade. Together, these results highlight the critical contribution of the collagen I-DDR1 interaction in the formation of an immune microenvironment that promotes PDAC metastasis.

Indexed as

Gene Expression Regulation, NeoplasticNeoplasms, ExperimentalAnimalsCarcinogenesisCarcinoma, Pancreatic DuctalCell Line, TumorCell MovementCell ProliferationDiscoidin Domain Receptor 1DNA, NeoplasmExtracellular TrapsHumansMiceMice, Inbred C57BLMice, NudeNeoplasm MetastasisDdr1 protein, mouseDiscoidin Domain Receptor 1DNA, NeoplasmCytokinesNeutrophilsOncologySignal transduction

Identifiers

PMID34237033
PMCPMC8492346
OpenAlexW3128351982

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.