Evidence map›Paper›PMID 11423990›Full record

ArticleOncogene2001

Soluble CD44 inhibits melanoma tumor growth by blocking cell surface CD44 binding to hyaluronic acid.

T Ahrens, J P Sleeman, C M Schempp, N Howells, M Hofmann, H Ponta, P Herrlich, J C Simon

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

62 citing papers in PubMed, 136 citations in OpenAlex.

  1. Trial
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  10. Article
  11. Hyaluronic Acid as a Modern Approach in Anticancer Therapy-Review.International journal of molecular sciences · 2022
    Review
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  14. Review
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2 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

8 authors at 2 institutions in 1 country.

T AhrensDepartment of Dermatology, University of Freiburg, Hauptstrasse 7, D-79104, Freiburg, Germany.
J P Sleeman
C M Schempp
N Howells
M Hofmann
H Ponta
P Herrlich
J C Simon
FZI Research Center for Information Technology · DEUniversity of Freiburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Proteolytic cleavage of the extracellular domain of CD44 from the surface of cells has been observed recently in different cell types. In cell culture supernatants of human melanoma cell lines a 70 kDa soluble CD44 protein (solCD44) was detected at concentrations of 250-300 ng/ml. Protease inhibitor studies revealed that serine proteases and metalloproteases are involved in the cleavage of CD44 from the surface of melanoma cells. To analyse a possible function of soluble CD44 a human malignant melanoma cell line was stably transfected with cDNAs encoding either wild type soluble CD44s or mutated forms with defective HA binding properties (CD44sR41A and CD44sR150A/R154A). Soluble CD44s almost completely inhibited hyaluronic acid binding by melanoma cells, whereas soluble CD44 mutated in the HA binding domain had no effect. When cultivated on hyaluronic acid, melanoma cell proliferation was induced by 30% for both the parental and the control transfected cells. This increase in proliferation was blocked completely in solCD44s-secreting transfectants, whereas solCD44sR41A and solCD44sR150A/R154A-secreting cells again showed hyaluronic acid-induced cell proliferation. These cell lines were subcutaneously injected into MF1 nu/nu mice to compare their growth as tumors in vivo. Compared to tumors derived from parental and control transfected cells, we observed a dramatic reduction of primary tumor growth with solCD44s expressing MM cells. Transfectants expressing solCD44s mutated in the HA binding domain in contrast developed fast-growing primary tumors. These results provide strong evidence that direct solCD44 interactions with hyaluronic acid interfere competitively with processes induced by hyaluronic acid binding to surface CD44. Autocrine, or drug-induced secretion of solCD44 by human melanoma cells may thus exert potent antitumoral effects in vivo.

Indexed as

AnimalsBinding, CompetitiveBinding SitesCell AdhesionCell DivisionCulture MediaGlycopeptidesHumansHyaluronan ReceptorsHyaluronic AcidMelanomaMelanoma, ExperimentalMetalloendopeptidasesMiceMice, NudeNeoplasm Proteins1,10-phenanthroline4-(2-aminoethyl)benzenesulfonylfluorideCulture MediaGlycopeptidesHyaluronan ReceptorsHyaluronic AcidMetalloendopeptidasesNeoplasm ProteinspepstatinPepstatinsPhenanthrolinesphosphoramidonProtease InhibitorsRecombinant Fusion ProteinsStreptomyces pepsin inhibitorSulfones

Identifiers

PMID11423990
OpenAlexW2045306157

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.