Evidence map›Paper›PMID 28153880›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2017

Tamoxifen Directly Inhibits Platelet Angiogenic Potential and Platelet-Mediated Metastasis.

Kelly E Johnson, Jodi A Forward, Mason D Tippy, Julia R Ceglowski, Saleh El-Husayni, Rajesh Kulenthirarajan, Kellie R Machlus, Erica L Mayer, Joseph E Italiano, Elisabeth M Battinelli

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PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 8% 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

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

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  9. Tamoxifen induces eryptosis through calcium accumulation and oxidative stress.Medical oncology (Northwood, London, England) · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Kelly E JohnsonFrom the Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (K.E.J., J.A.F., M.D.T., J.R.C., S.E.-H., R.K., K.R.M., J.E.I., E.M.B.); Department of Medicine, Harvard Medical School, Boston, MA (K.E.J., K.R.M., E.L.M., J.E.I., E.M.B.); Vascular Biology Program, Department of Surgery, Children's Hospital Boston, MA (J.E.I.); and Division of Hematology, Dana-Farber Cancer Institute, Boston, MA (E.L.M.).
Jodi A ForwardFrom the Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (K.E.J., J.A.F., M.D.T., J.R.C., S.E.-H., R.K., K.R.M., J.E.I., E.M.B.); Department of Medicine, Harvard Medical School, Boston, MA (K.E.J., K.R.M., E.L.M., J.E.I., E.M.B.); Vascular Biology Program, Department of Surgery, Children's Hospital Boston, MA (J.E.I.); and Division of Hematology, Dana-Farber Cancer Institute, Boston, MA (E.L.M.).
Mason D TippyFrom the Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (K.E.J., J.A.F., M.D.T., J.R.C., S.E.-H., R.K., K.R.M., J.E.I., E.M.B.); Department of Medicine, Harvard Medical School, Boston, MA (K.E.J., K.R.M., E.L.M., J.E.I., E.M.B.); Vascular Biology Program, Department of Surgery, Children's Hospital Boston, MA (J.E.I.); and Division of Hematology, Dana-Farber Cancer Institute, Boston, MA (E.L.M.).
Julia R CeglowskiFrom the Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (K.E.J., J.A.F., M.D.T., J.R.C., S.E.-H., R.K., K.R.M., J.E.I., E.M.B.); Department of Medicine, Harvard Medical School, Boston, MA (K.E.J., K.R.M., E.L.M., J.E.I., E.M.B.); Vascular Biology Program, Department of Surgery, Children's Hospital Boston, MA (J.E.I.); and Division of Hematology, Dana-Farber Cancer Institute, Boston, MA (E.L.M.).
Saleh El-HusayniFrom the Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (K.E.J., J.A.F., M.D.T., J.R.C., S.E.-H., R.K., K.R.M., J.E.I., E.M.B.); Department of Medicine, Harvard Medical School, Boston, MA (K.E.J., K.R.M., E.L.M., J.E.I., E.M.B.); Vascular Biology Program, Department of Surgery, Children's Hospital Boston, MA (J.E.I.); and Division of Hematology, Dana-Farber Cancer Institute, Boston, MA (E.L.M.).
Rajesh KulenthirarajanFrom the Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (K.E.J., J.A.F., M.D.T., J.R.C., S.E.-H., R.K., K.R.M., J.E.I., E.M.B.); Department of Medicine, Harvard Medical School, Boston, MA (K.E.J., K.R.M., E.L.M., J.E.I., E.M.B.); Vascular Biology Program, Department of Surgery, Children's Hospital Boston, MA (J.E.I.); and Division of Hematology, Dana-Farber Cancer Institute, Boston, MA (E.L.M.).
Kellie R MachlusFrom the Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (K.E.J., J.A.F., M.D.T., J.R.C., S.E.-H., R.K., K.R.M., J.E.I., E.M.B.); Department of Medicine, Harvard Medical School, Boston, MA (K.E.J., K.R.M., E.L.M., J.E.I., E.M.B.); Vascular Biology Program, Department of Surgery, Children's Hospital Boston, MA (J.E.I.); and Division of Hematology, Dana-Farber Cancer Institute, Boston, MA (E.L.M.).
Erica L MayerFrom the Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (K.E.J., J.A.F., M.D.T., J.R.C., S.E.-H., R.K., K.R.M., J.E.I., E.M.B.); Department of Medicine, Harvard Medical School, Boston, MA (K.E.J., K.R.M., E.L.M., J.E.I., E.M.B.); Vascular Biology Program, Department of Surgery, Children's Hospital Boston, MA (J.E.I.); and Division of Hematology, Dana-Farber Cancer Institute, Boston, MA (E.L.M.).
Joseph E ItalianoFrom the Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (K.E.J., J.A.F., M.D.T., J.R.C., S.E.-H., R.K., K.R.M., J.E.I., E.M.B.); Department of Medicine, Harvard Medical School, Boston, MA (K.E.J., K.R.M., E.L.M., J.E.I., E.M.B.); Vascular Biology Program, Department of Surgery, Children's Hospital Boston, MA (J.E.I.); and Division of Hematology, Dana-Farber Cancer Institute, Boston, MA (E.L.M.).
Elisabeth M BattinelliFrom the Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (K.E.J., J.A.F., M.D.T., J.R.C., S.E.-H., R.K., K.R.M., J.E.I., E.M.B.); Department of Medicine, Harvard Medical School, Boston, MA (K.E.J., K.R.M., E.L.M., J.E.I., E.M.B.); Vascular Biology Program, Department of Surgery, Children's Hospital Boston, MA (J.E.I.); and Division of Hematology, Dana-Farber Cancer Institute, Boston, MA (E.L.M.). ebattinelli@partners.org.
Harvard University · USBoston Children's Hospital · US

Funding

Cytoskeletal Mechanisms of Platelet FormationR01HL068130 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI ITALIANO, JOSEPH E · 2001 to 2021
$8.1M
Training Program in Molecular HematologyT32HL116324 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI NANCY BERLINER · 2013 to 2026
$7.4M
How does malignancy subvert platelet and megakaryocytic biology?R01CA200748 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BATTINELLI, ELISABETH M, ITALIANO, JOSEPH E · 2017 to 2021
$2.7M
Defining the Mechanisms by Which Plateletes Regulate AngiogenesisK08HL097070 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI BATTINELLI, ELISABETH M · 2009 to 2013
$689k
NCI NIH HHS R01 CA200748NHLBI NIH HHS K08 HL097070NHLBI NIH HHS R01 HL068130NHLBI NIH HHS T32 HL116324
6 · The paper itself

Abstract

objectivePlatelets, which are mainly known for their role in hemostasis, are now known to play a crucial role in metastasis. Tamoxifen is a selective estrogen receptor modulator that is widely used for the treatment of breast cancer. Tamoxifen and its metabolites have been shown to directly impact platelet function, suggesting that this drug has additional mechanisms of action. The purpose of this study was to determine whether tamoxifen exerts antitumor effects through direct platelet inhibition. APPROACH AND

resultsThis study found that pretreatment with tamoxifen leads to a significant inhibition of platelet activation. Platelets exposed to tamoxifen released significantly lower amounts of proangiogenic regulator vascular endothelial growth factor. In vitro angiogenesis assays confirmed that tamoxifen pretreatment led to diminished capillary tube formation and decreased endothelial migration. Tamoxifen and its metabolite, 4-hydroxytamoxifen, also significantly inhibited the ability of platelets to promote metastasis in vitro. Using a membrane-based array, we identified several proteins associated with angiogenesis metastasis that were lower in activated releasate from tamoxifen-treated platelets, including angiogenin, chemokine (C-X-C motif) ligand 1, chemokine (C-C motif) ligand 5, epidermal growth factor, chemokine (C-X-C motif) ligand 5, platelet-derived growth factor dimeric isoform BB, whereas antiangiogenic angiopoietin-1 was elevated. Platelets isolated from patients on tamoxifen maintenance therapy were also found to have decreased activation responses, diminished vascular endothelial growth factor release, and lower angiogenic and metastatic potential.

conclusionsWe demonstrate that tamoxifen and its metabolite 4-hydroxytamoxifen directly alter platelet function leading to decreased angiogenic and metastatic potential. Furthermore, this study supports the idea of utilizing targeted platelet therapies to inhibit the platelet's role in angiogenesis and malignancy.

Indexed as

Angiogenesis InhibitorsBlood PlateletsBreast NeoplasmsCell MovementCell ProliferationCoculture TechniquesFemaleHumansHuman Umbilical Vein Endothelial CellsMCF-7 CellsNeoplasm MetastasisNeovascularization, PhysiologicPlatelet ActivationPlatelet Aggregation InhibitorsSignal TransductionTamoxifenafimoxifeneAngiogenesis InhibitorsPlatelet Aggregation InhibitorsTamoxifenVascular Endothelial Growth Factor AVEGFA protein, humanblood plateletsneoplasm metastasisplatelet activationtamoxifen

Identifiers

PMID28153880
PMCPMC5364056
OpenAlexW2584450063

What OpenQuestion holds

Textmetadata
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Registered trials

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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.