Evidence map›Paper›PMID 25769726›Full record

ArticleCancer research2015

Induction of Vasculogenic Mimicry Overrides VEGF-A Silencing and Enriches Stem-like Cancer Cells in Melanoma.

Caroline I Schnegg, Moon Hee Yang, Subrata K Ghosh, Mei-Yu Hsu

Abstract read
In one paragraph

Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 2 pooled it
3.6field-weighted citation impact, top 6% 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

61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 99 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. International journal of molecular sciences · 2024
    Article
  12. Article
  13. Vascular mimicry as a facilitator of melanoma brain metastasis.Cellular and molecular life sciences : CMLS · 2024
    Article
  14. Article
  15. Mechanisms of angiogenesis in tumour.Frontiers in oncology · 2024
    Review
  16. Article
  17. An Overview of Angiogenesis in Bladder Cancer.Current oncology reports · 2023
    Review
  18. Article
  19. Article
  20. Review

1 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

4 authors at 2 institutions in 1 country.

Caroline I SchneggDepartment of Dermatology, Boston University Medical Center, Boston, Massachusetts.
Moon Hee YangDepartment of Dermatology, Boston University Medical Center, Boston, Massachusetts.
Subrata K GhoshDepartment of Dermatology, Boston University Medical Center, Boston, Massachusetts.
Mei-Yu HsuDepartment of Dermatology, Boston University Medical Center, Boston, Massachusetts. meiyuhsu@bu.edu.
Boston Medical Center · USUniversity Medical Center · US

Funding

BMP7 in melanoma niche morphogenesis and homeostasisR01CA138649 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI HSU, MEI-YU · 2010 to 2014
$1.6M
NCI NIH HHS R01 CA138649NCI NIH HHS R01CA138649
6 · The paper itself

Abstract

The basis for resistance to VEGF inhibition is not fully understood despite its clinical importance. In this study, we examined the adaptive response to VEGF-A inhibition by a loss-of-function analysis using plasmid-based shRNA. Tumor xenografts that initially responded to VEGF-A inhibition underwent an adaptation in vivo, leading to acquired resistance. VEGF-A blockade in tumors was associated with HIF1α expression and an increase in CD144(+) vasculogenic mimicry (VM), leading to formation of channels displaying Tie-1 and MMP-2 upregulation. CD133(+) and CD271(+) melanoma stem-like cells (MSLC) accumulated in the perivascular niche. Tumor xenografts of melanoma cell populations that were intrinsically resistant to VEGF-A blockade did not exhibit any of these features, compared with nontarget control counterparts. Thus, melanomas that are initially sensitive to VEGF-A blockade acquire adaptive resistance by adopting VM as an alternate angiogenic strategy, thereby enriching for deposition of MSLC in the perivascular niche through an HIF1α-dependent process. Conversely, melanomas that are intrinsically resistant to VEGF-A blockade do not show any evidence of compensatory survival mechanisms that promote MSLC accumulation. Our work highlights the potential risk of anti-VEGF treatments owing to a selective pressure for an adaptive resistance mechanism that empowers the development of stem-like cancer cells, with implications for how to design combination therapies that can improve outcomes in patients.

Indexed as

AnimalsCell CountCell ProliferationDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansMelanomaMiceMice, Inbred C57BLMice, SCIDNeoplastic Stem CellsNeovascularization, PathologicRNA InterferenceRNA, Small InterferingSkin NeoplasmsRNA, Small InterferingVascular Endothelial Growth Factor A

Identifiers

PMID25769726
PMCPMC4401656
OpenAlexW2149518598

What OpenQuestion holds

Textmetadata
LicenceTDM
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.