Evidence map›Paper›PMID 21194429›Full record

ArticleMolecular cancer2010

VEGF₁₂₁b and VEGF₁₆₅b are weakly angiogenic isoforms of VEGF-A.

Raúl Catena, Leyre Larzabal, Marta Larrayoz, Eva Molina, Jose Hermida, Jackeline Agorreta, Ramon Montes, Ruben Pio, Luis M Montuenga, Alfonso Calvo

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
1.9field-weighted citation impact, top 15% 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

42 citing papers in PubMed, 70 citations in OpenAlex.

  1. VEGFAngiogenesis · 2026
    Article
  2. Quantification of vitreous VEGF-A121 and VEGF-A165 using an isoform-specific ELISA in proliferative diabetic retinopathy.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
    Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. The VEGF/VEGFR Axis Revisited: Implications for Cancer Therapy.International journal of molecular sciences · 2022
    Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Hypoxia-induced alternative splicing: the 11th Hallmark of Cancer.Journal of experimental & clinical cancer research : CR · 2020
    Review
  19. Review
  20. VEGFOncogene · 2019
    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

10 authors at 1 institution in 1 country.

Raúl CatenaLaboratory of Novel Therapeutic Targets, Division of Oncology, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Leyre Larzabal
Marta Larrayoz
Eva Molina
Jose Hermida
Jackeline Agorreta
Ramon Montes
Ruben Pio
Luis M Montuenga
Alfonso Calvo
Universidad de Navarra · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDifferent isoforms of VEGF-A (mainly VEGF₁₂₁, VEGF₁₆₅ and VEGF189) have been shown to display particular angiogenic properties in the generation of a functional tumor vasculature. Recently, a novel class of VEGF-A isoforms, designated as VEGF(xxx)b, generated through alternative splicing, have been described. Previous studies have suggested that these isoforms may inhibit angiogenesis. In the present work we have produced recombinant VEGF₁₂₁/₁₆₅b proteins in the yeast Pichia pastoris and constructed vectors to overexpress these isoforms and assess their angiogenic potential.

resultsRecombinant VEGF₁₂₁/₁₆₅b proteins generated either in yeasts or mammalian cells activated VEGFR2 and its downstream effector ERK1/2, although to a lesser extent than VEGF₁₆₅. Furthermore, treatment of endothelial cells with VEGF₁₂₁/₁₆₅b increased cell proliferation compared to untreated cells, although such stimulation was lower than that induced by VEGF₁₆₅. Moreover, in vivo angiogenesis assays confirmed angiogenesis stimulation by VEGF₁₂₁/₁₆₅b isoforms. A549 and PC-3 cells overexpressing VEGF₁₂₁b or VEGF₁₆₅b (or carrying the PCDNA3.1 empty vector, as control) and xenotransplanted into nude mice showed increased tumor volume and angiogenesis compared to controls. To assess whether the VEGF(xxx)b isoforms are differentially expressed in tumors compared to healthy tissues, immunohistochemical analysis was conducted on a breast cancer tissue microarray. A significant increase (p < 0.05) in both VEGF(xxx)b and total VEGF-A protein expression in infiltrating ductal carcinomas compared to normal breasts was observed. A positive significant correlation (r = 0.404, p = 0.033) between VEGF(xxx)b and total VEGF-A was found.

conclusionsOur results demonstrate that VEGF₁₂₁/₁₆₅b are not anti-angiogenic, but weakly angiogenic isoforms of VEGF-A. In addition, VEGF(xxx)b isoforms are up-regulated in breast cancer in comparison with non malignant breast tissues. These results are to be taken into account when considering a possible use of VEGF₁₂₁/₁₆₅b-based therapies in patients.

Indexed as

AnimalsBlotting, WesternCell LineCell Line, TumorCell ProliferationHumansImmunohistochemistryMiceMice, NudeNeovascularization, PathologicPhosphorylationPichiaProtein IsoformsRecombinant ProteinsVascular Endothelial Growth Factor AProtein IsoformsRecombinant ProteinsVascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID21194429
PMCPMC3022671
OpenAlexW2041817351

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.