Evidence map›Paper›PMID 30302660›Full record

ArticleStem cell reviews and reports2019

Bioactive Phospholipids Enhance Migration and Adhesion of Human Leukemic Cells by Inhibiting Heme Oxygenase 1 (HO-1) and Inducible Nitric Oxygenase Synthase (iNOS) in a p38 MAPK-Dependent Manner.

Ahmed Abdelbaset-Ismail, Monika Cymer, Sylwia Borkowska-Rzeszotek, Katarzyna Brzeźniakiewicz-Janus, Pranela Rameshwar, Sham S Kakar, Janina Ratajczak, Mariusz Z Ratajczak

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reviews and reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

20 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Role of Ceramide Kinase/C1P in the Regulation of Cell Growth and Survival.International journal of molecular sciences · 2025
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  18. Lipid mediators of insulin signaling in diabetic kidney disease.American journal of physiology. Renal physiology · 2019
    Review
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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

8 authors at 6 institutions in 3 countries.

Ahmed Abdelbaset-IsmailStem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Rm. 107, Louisville, KY, 40202, USA.
Monika CymerCenter for Preclinical Research and Technology, Department of Regenerative Medicine, Warsaw Medical University, Warsaw, Poland.
Sylwia Borkowska-RzeszotekDepartment of Physiology, Pomeranian Medical University, Szczecin, Poland.
Katarzyna Brzeźniakiewicz-JanusDepartment of Hematology, Multi-specialist Hospital, University of Zielona Gora, Gorzow Wlkp, Poland.
Pranela RameshwarRutgers New Jersey Medical School, Newark, NJ, USA.
Sham S KakarStem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Rm. 107, Louisville, KY, 40202, USA.
Janina RatajczakStem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Rm. 107, Louisville, KY, 40202, USA.
Mariusz Z RatajczakStem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 S. Floyd Street, Rm. 107, Louisville, KY, 40202, USA. mzrata01@louisville.edu.
Medical University of Warsaw · PLUniversity of Louisville · USPomeranian Medical University · PLRutgers New Jersey Medical SchoolUniversity of Zielona Góra · PLZagazig University · EG

Funding

Novel mechanisms involving complement cascade in stem cell traffickingR01DK074720 · NIDDK · UNIVERSITY OF LOUISVILLE · PI RATAJCZAK, MARIUSZ Z · 2007 to 2020
$4.1M
BIOACTIVE LIPIDS IN STEM CELL HOMING AND MOBILIZATIONR01HL112788 · NHLBI · UNIVERSITY OF LOUISVILLE · PI RATAJCZAK, MARIUSZ Z · 2013 to 2016
$1.5M
NHLBI NIH HHS R01 HL112788NHLBI NIH HHS R01HL112788NIDDK NIH HHS 2R01 DK074720NIDDK NIH HHS R01 DK074720
6 · The paper itself

Abstract

Bioactive phospholipids, including sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P), lysophosphatidylcholine (LPC), and its derivative lysophosphatidic acid (LPA), have emerged as important mediators regulating the trafficking of normal and cancer cells. While the role of S1P in regulating migration of hematopoietic cells is well established, in this work we compared its biological effects to the effects of C1P, LPC, and LPA. We employed 10 human myeloid and lymphoid cell lines as well as blasts from AML patients. We observed that human leukemic cells express functional receptors for phospholipids and respond to stimulation by phosphorylation of p42/44 MAPK and AKT. We also found that bioactive phospholipids enhanced cell migration and adhesion of leukemic cells by downregulating expression of HO-1 and iNOS in a p38 MAPK-dependent manner but did not affect cell proliferation. By contrast, downregulation of p38 MAPK by SB203580 enhanced expression of HO-1 and iNOS and decreased migration of leukemic cells in vitro and their seeding efficiency to vital organs in vivo after injection into immunodeficient mice. Based on these findings, we demonstrate that, besides S1P, human leukemic cells also respond to C1P, LPC, and LPA. Since the prometastatic effects of bioactive phospholipids in vivo were mediated, at least in part, by downregulating HO-1 and iNOS expression in a p38 MAPK-dependent manner, we propose that inhibitors of p38 MAPK or stimulators of HO-1 activity will find application in inhibiting the spread of leukemic cells in response to bioactive phospholipids.

Indexed as

AnimalsBlast CrisisCell AdhesionCell Line, TumorCell MovementCell ProliferationCeramidesFibronectinsHematopoietic Stem CellsHeme Oxygenase-1HumansLeukemiaLysophospholipidsMice, SCIDNitric Oxide Synthase Type IIp38 Mitogen-Activated Protein Kinasesceramide 1-phosphateCeramidesFibronectinsHeme Oxygenase-1LysophospholipidsNitric Oxide Synthase Type IIp38 Mitogen-Activated Protein KinasesPhospholipidsReceptors, Cell SurfaceSphingosinesphingosine 1-phosphateC1PHO-1HO-1 activatorsLeukemiaLPALPCp38 MAPKS1P

Identifiers

PMID30302660
PMCPMC6366663
OpenAlexW2896678476

What OpenQuestion holds

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LicenceCC BY
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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.