Evidence map›Paper›PMID 11752393›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2002

Tumor attenuation by combined heparan sulfate and polyamine depletion.

Mattias Belting, Lubor Borsig, Mark M Fuster, Jillian R Brown, Lo Persson, Lars-Ake Fransson, Jeffrey D Esko

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

32 citing papers in PubMed, 119 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Cancer Cell Glycocalyx and Its Significance in Cancer Progression.International journal of molecular sciences · 2018
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity.Proceedings of the National Academy of Sciences of the United States of America · 2013
    Article
  14. Article
  15. Article
  16. DFMO: targeted risk reduction therapy for colorectal neoplasia.Best practice & research. Clinical gastroenterology · 2011
    Review
  17. Article
  18. Article
  19. Current status of the polyamine research field.Methods in molecular biology (Clifton, N.J.) · 2011
    Review
  20. Article
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

7 authors at 1 institution in 1 country.

Mattias BeltingDepartment of Cell and Molecular Biology, Biomedical Center C13, Lund University, P.O.B. 94, S-221 84 Lund, Sweden.
Lubor Borsig
Mark M Fuster
Jillian R Brown
Lo Persson
Lars-Ake Fransson
Jeffrey D Esko
Lund University · SE

Funding

GENETIC CONTROL OF PROTEOGLYCAN METABOLISMR37GM033063 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D · 2000 to 2010
$3.9M
LIPID METABOLISM IN ANIMAL CELLSR01GM033063 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D · 1985 to 2019
$3.4M
Heparan Sulfate--a Novel Target for Cancer TherapeuticsU01CA091290 · NCI · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI ESKO, JEFFREY D · 2001 to 2004
$1.8M
NCI NIH HHS CA91290NCI NIH HHS U01 CA091290NIGMS NIH HHS GM33063NIGMS NIH HHS R01 GM033063NIGMS NIH HHS R37 GM033063
6 · The paper itself

Abstract

Cells depend on polyamines for growth and their depletion represents a strategy for the treatment of cancer. Polyamines assemble de novo through a pathway sensitive to the inhibitor, alpha-difluoromethylornithine (DFMO). However, the presence of cell-surface heparan sulfate proteoglycans may provide a salvage pathway for uptake of circulating polyamines, thereby sparing cells from the cytostatic effect of DFMO. Here we show that genetic or pharmacologic manipulation of proteoglycan synthesis in the presence of DFMO inhibits cell proliferation in vitro and in vivo. In cell culture, mutant cells lacking heparan sulfate were more sensitive to the growth inhibitory effects of DFMO than wild-type cells or mutant cells transfected with the cDNA for the missing biosynthetic enzyme. Moreover, extracellular polyamines did not restore growth of mutant cells, but completely reversed the inhibitory effect of DFMO in wild-type cells. In a mouse model of experimental metastasis, DFMO provided in the water supply also dramatically diminished seeding and growth of tumor foci in the lungs by heparan sulfate-deficient mutant cells compared with the controls. Wild-type cells also formed tumors less efficiently in mice fed both DFMO and a xylose-based inhibitor of heparan sulfate proteoglycan assembly. The effect seemed to be specific for heparan sulfate, because a different xyloside known to affect only chondroitin sulfate did not inhibit tumor growth. Hence, combined inhibition of heparan sulfate assembly and polyamine synthesis may represent an additional strategy for cancer therapy.

Indexed as

AnimalsAntineoplastic AgentsCHO CellsCricetinaeDNA, ComplementaryDose-Response Relationship, DrugEflornithineEnzyme InhibitorsFemaleGlucuronosyltransferaseHeparan SulfateMiceMice, SCIDModels, BiologicalModels, GeneticNeoplasm MetastasisAntineoplastic AgentsDNA, ComplementaryEflornithineEnzyme Inhibitorsgalactosylgalactoylxylosylprotein 3-beta-glucuronosyltransferaseGlucuronosyltransferaseHeparan SulfatePolyaminesProteoglycansSpermine

Identifiers

PMID11752393
PMCPMC117567
OpenAlexW2120240705

What OpenQuestion holds

Textmetadata
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.