Evidence map›Paper›PMID 19234131›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2009

Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR.

Khalid Al-Nedawi, Brian Meehan, Robert S Kerbel, Anthony C Allison, Janusz Rak

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 367 papers.

0numbers the graph read from it
0cells of the map it votes in
367citing papers in PubMed
13.6field-weighted citation impact, top 1% 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

367 citing papers in PubMed, 653 citations in OpenAlex.

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  17. Current Understanding of the Exosomes and Their Associated Biomolecules in the Glioblastoma Biology, Clinical Treatment, and Diagnosis.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
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307 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

5 authors at 3 institutions in 1 country.

Khalid Al-NedawiMontreal Children's Hospital Research Institute, McGill University, Montreal, QC, Canada H3Z 2Z3.
Brian Meehan
Robert S Kerbel
Anthony C Allison
Janusz Rak
McGill University · CAMontreal Children's Hospital · CASunnybrook Health Science Centre · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Activated EGF receptor (EGFR) plays an oncogenic role in several human malignancies. Although the intracellular effects of EGFR are well studied, its ability to induce and modulate tumor angiogenesis is less understood. We found previously that oncogenic EGFR can be shed from cancer cells as cargo of membrane microvesicles (MVs), which can interact with surfaces of other cells. Here we report that MVs produced by human cancer cells harboring activated EGFR (A431, A549, DLD-1) can be taken up by cultured endothelial cells, in which they elicit EGFR-dependent responses, including activation of MAPK and Akt pathways. These responses can be blocked by annexin V and its homodimer, Diannexin, both of which cloak phosphatidylserine residues on the surfaces of MVs. Interestingly, the intercellular EGFR transfer is also accompanied by the onset of VEGF expression in endothelial cells and by autocrine activation of its key signaling receptor (VEGF receptor-2). In A431 human tumor xenografts in mice, angiogenic endothelial cells stain positively for human EGFR and phospho-EGFR, while treatment with Diannexin leads to a reduction of tumor growth rate and microvascular density. Thus, we propose that oncogene-containing tumor cell-derived MVs could act as a unique form of angiogenesis-modulating stimuli and are capable of switching endothelial cells to act in an autocrine mode.

Indexed as

Autocrine CommunicationAnimalsCell LineCell MembraneCell ProliferationEndothelial CellsErbB ReceptorsHumansMiceNeoplasmsNeovascularization, PathologicPhosphatidylserinesSignal TransductionVascular Endothelial Growth Factor AEGFR protein, humanErbB ReceptorsPhosphatidylserinesVascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID19234131
PMCPMC2656159
OpenAlexW1984557698

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.