Evidence map›Paper›PMID 26243191›Full record

ArticleScience signaling2015

Semaphorin 3D autocrine signaling mediates the metastatic role of annexin A2 in pancreatic cancer.

Kelly Foley, Agnieszka A Rucki, Qian Xiao, Donger Zhou, Ashley Leubner, Guanglan Mo, Jennifer Kleponis, Annie A Wu, Rajni Sharma, Qingguang Jiang and 6 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07331532 (PET Imaging Study of 68Ga-PFA2 Probe for Annexin A2-Positive Tumors), which is not on this map. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed
3.5field-weighted citation impact, top 7% 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.

NCT07331532 recruitingnot on this mapstarted 2025, after this paper: background citation

PET Imaging Study of 68Ga-PFA2 Probe for Annexin A2-Positive Tumors

Typeobservational_patient_registrySponsorPeking University First HospitalRan2025 to 2027Enrolled10ConditionsBreast Neoplasms、Lung Neoplasms、Pancreatic Neoplasms
3 · Its place in the literature

Who cites it

79 citing papers in PubMed, 130 citations in OpenAlex.

  1. Article
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  7. Interleukin 6 Drives Durable T Cell-Mediated Immunity to Pancreatic Cancer.Cellular and molecular gastroenterology and hepatology · 2026
    Article
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19 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

16 authors at 4 institutions in 1 country.

Kelly FoleySidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Agnieszka A RuckiSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Qian XiaoSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Donger ZhouSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Ashley LeubnerSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Guanglan MoSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Skip Viragh Center for Pancreatic Cancer, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Jennifer KleponisSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Annie A WuSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Rajni SharmaDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Qingguang JiangDepartment of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Robert A AndersSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Christine A Iacobuzio-DonahueSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Katherine A HajjarDepartment of Pediatrics, Weill Cornell Medical College, New York, NY 10065, USA.
Anirban MaitraSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Elizabeth M JaffeeSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Skip Viragh Center for Pancreatic Cancer, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Lei ZhengSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Skip Viragh Center for Pancreatic Cancer, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. lzheng6@jhmi.edu.
Johns Hopkins Medicine · USSidney Kimmel Comprehensive Cancer Center · USJohns Hopkins University · USCornell University · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
Tumor Antigens for Individual Signatures and TherapyP50CA062924 · NCI · JOHNS HOPKINS UNIVERSITY · PI LENNON, ANNE MARIE · 1993 to 2022
$54.6M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007309 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI COX, ANDREA L · 1985 to 2019
$43.2M
Interrogate the interaction between tumor cells and nerves in the tumor microenvironment of pancreatic cancerR01CA169702 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI ZHENG, LEI · 2013 to 2023
$3.6M
Dissecting the mechanisms of immune tolerance within the pancreatic tumor's microK23CA148964 · NCI · JOHNS HOPKINS UNIVERSITY · PI ZHENG, LEI · 2010 to 2014
$888k
NCI NIH HHS K23 CA148964NCI NIH HHS K23 CA148964-01NCI NIH HHS P30 CA006973NCI NIH HHS P30CA006973NCI NIH HHS P50 CA062924NCI NIH HHS P50CA062924NCI NIH HHS R01 CA169702NHLBI NIH HHS HL42093NIGMS NIH HHS T32 GM007309
6 · The paper itself

Abstract

Most patients with pancreatic ductal adenocarcinoma (PDA) present with metastatic disease at the time of diagnosis or will recur with metastases after surgical treatment. Semaphorin-plexin signaling mediates the migration of neuronal axons during development and of blood vessels during angiogenesis. The expression of the gene encoding semaphorin 3D (Sema3D) is increased in PDA tumors, and the presence of antibodies against the pleiotropic protein annexin A2 (AnxA2) in the sera of some patients after surgical resection of PDA is associated with longer recurrence-free survival. By knocking out AnxA2 in a transgenic mouse model of PDA (KPC) that recapitulates the progression of human PDA from premalignancy to metastatic disease, we found that AnxA2 promoted metastases in vivo. The expression of AnxA2 promoted the secretion of Sema3D from PDA cells, which coimmunoprecipitated with the co-receptor plexin D1 (PlxnD1) on PDA cells. Mouse PDA cells in which SEMA3D was knocked down or ANXA2-null PDA cells exhibited decreased invasive and metastatic potential in culture and in mice. However, restoring Sema3D in AnxA2-null cells did not entirely rescue metastatic behavior in culture and in vivo, suggesting that AnxA2 mediates additional prometastatic mechanisms. Patients with primary PDA tumors that have abundant Sema3D have widely metastatic disease and decreased survival compared to patients with tumors that have relatively low Sema3D abundance. Thus, AnxA2 and Sema3D may be new therapeutic targets and prognostic markers of metastatic PDA.

Indexed as

AnimalsAnnexin A2Autocrine CommunicationBlotting, WesternCarcinoma, Pancreatic DuctalFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansIntracellular Signaling Peptides and ProteinsMembrane GlycoproteinsMice, 129 StrainMice, Inbred C57BLMice, KnockoutMice, TransgenicMicroscopy, FluorescenceAnnexin A2Intracellular Signaling Peptides and ProteinsMembrane GlycoproteinsNerve Tissue ProteinsPlxnd1 protein, mouseSema 3D protein, mouseSemaphorins

Identifiers

PMID26243191
PMCPMC4811025
OpenAlexW2177984400

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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.