Evidence map›Paper›PMID 22904678›Full record

ArticleNeoplasia (New York, N.Y.)2012

The effect of bevacizumab on human malignant melanoma cells with functional VEGF/VEGFR2 autocrine and intracrine signaling loops.

Una Adamcic, Karolina Skowronski, Craig Peters, Jodi Morrison, Brenda L Coomber

Open access · goldAbstract read
In one paragraph

Article in Neoplasia (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
2.4field-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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. WNT5A-ROR2 axis mediates VEGF dependence of BRAF mutant melanoma.Cellular oncology (Dordrecht, Netherlands) · 2023
    Article
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  11. sFRP2 Supersedes VEGF as an Age-related Driver of Angiogenesis in Melanoma, Affecting Response to Anti-VEGF Therapy in Older Patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
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  12. 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

5 authors at 1 institution in 1 country.

Una AdamcicDepartment of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada.
Karolina Skowronski
Craig Peters
Jodi Morrison
Brenda L Coomber
University of Guelph · CA

Funding

Canadian Institutes of Health Research MOP-81213
6 · The paper itself

Abstract

Receptors for the angiogenic factor VEGF are expressed by tumor cancer cells including melanoma, although their functionality remains unclear. Paired human melanoma cell lines WM115 and WM239 were used to investigate differences in expression and functionality of VEGF and VEGFR2 in vitro and in vivo with the anti-VEGF antibody bevacizumab. Both WM115 and WM239 cells expressed VEGF and VEGFR2, the levels of which were modulated by hypoxia. Detection of native and phosphorylated VEGFR2 in subcellular fractions under serum-free conditions showed the presence of a functional autocrine as well as intracrine VEGF/VEGFR2 signaling loops. Interestingly, treatment of WM115 and WM239 cells with increasing doses of bevacizumab (0-300 µg/ml) in vitro did not show any significant inhibition of VEGFR2 phosphorylation. Small-molecule tyrosine kinase inhibitor, sunitinib, caused an inhibition of VEGFR2 phosphorylation in WM239 but not in WM115 cells. An increase in cell proliferation was observed in WM115 cells treated with bevacizumab, whereas sunitinib inhibited proliferation. When xenografted to immune-deficient mice, we found bevacizumab to be an effective antiangiogenic but not antitumorigenic agent for both cell lines. Because bevacizumab is unable to neutralize murine VEGF, this supports a paracrine angiogenic response. We propose that the failure of bevacizumab to generate an antitumorigenic effect may be related to its generation of enhanced autocrine/intracrine signaling in the cancer cells themselves. Collectively, these results suggest that, for cancers with intracrine VEGF/ VEGFR2 signaling loops, small-molecule inhibitors of VEGFR2 may be more effective than neutralizing antibodies at disease control.

Indexed as

Angiogenesis InhibitorsAnimalsAntibodies, Monoclonal, HumanizedAutocrine CommunicationBevacizumabCell HypoxiaCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMelanomaMiceMice, NudePhosphorylationSignal TransductionAngiogenesis InhibitorsAntibodies, Monoclonal, HumanizedBevacizumabVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2

Identifiers

PMID22904678
PMCPMC3421957
OpenAlexW2130059802

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.