Evidence map›Paper›PMID 23227231›Full record

ArticlePloS one2012

Arresten, a collagen-derived angiogenesis inhibitor, suppresses invasion of squamous cell carcinoma.

Mari Aikio, Ilkka Alahuhta, Sini Nurmenniemi, Juho Suojanen, Riitta Palovuori, Susanna Teppo, Timo Sorsa, Carlos López-Otín, Taina Pihlajaniemi, Tuula Salo and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.8field-weighted citation impact, top 17% 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

23 citing papers in PubMed, 60 citations in OpenAlex.

  1. The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025
    Review
  2. Article
  3. Beyond classical collagen: basement membrane collagen IV in age-associated lung diseases.European respiratory review : an official journal of the European Respiratory Society · 2025
    Review
  4. The Multifaced Role of Collagen in Cancer Development and Progression.International journal of molecular sciences · 2024
    Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Extracellular matrix-derived peptides in tissue remodeling and fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2020
    Review
  15. Extracellular matrix dynamics in vascular remodeling.American journal of physiology. Cell physiology · 2020
    Review
  16. Review
  17. Regulation of spermatogenesis by a local functional axis in the testis: role of the basement membrane-derived noncollagenous 1 domain peptide.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017
    Article
  18. Extracellular Matrix, a Hard Player in Angiogenesis.International journal of molecular sciences · 2016
    Review
  19. Review
  20. Review
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

12 authors at 3 institutions in 2 countries.

Mari AikioOulu Center for Cell-Matrix Research, University of Oulu, Oulu, Finland.
Ilkka Alahuhta
Sini Nurmenniemi
Juho Suojanen
Riitta Palovuori
Susanna Teppo
Timo Sorsa
Carlos López-Otín
Taina Pihlajaniemi
Tuula Salo
Ritva Heljasvaara
Pia Nyberg
University of Oulu · FIUniversity of Helsinki · FIUniversidad de Oviedo · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The turnover of extracellular matrix liberates various cryptic molecules with novel biological activity. Among these are the collagen-derived anti-angiogenic fragments, some of which are suggested to affect carcinoma cells also directly. Arresten is an endogenous angiogenesis inhibitor that is derived from the non-collagenous domain of the basement membrane collagen IV α1 chain. As the mere prevention of tumor angiogenesis leads to hypoxia that can result in selection of more aggressive cell types and reduces the efficacy of chemotherapy, we aimed here to elucidate how arresten influences the aggressive human carcinoma cells. Arresten efficiently inhibited migration and invasion of HSC-3 tongue carcinoma cells in culture and in an organotypic model. Subcutaneous Arr-HSC xenografts grew markedly more slowly in nude mice and showed reduced tumor cell proliferation, vessel density and local invasiveness. In the organotypic assay, HSC-3 cells overproducing arresten (Arr-HSC) showed induction of cell death. In monolayer culture the Arr-HSC cells grew in aggregated cobblestone-like clusters and, relative to the control cells, showed increased expression and localization of epithelial marker E-cadherin in cell-cell contacts. Application of electric cell-substrate impedance sensing (ECIS) further supported our observations on altered morphology and motility of the Arr-HSC cells. Administration of a function-blocking α1 integrin antibody abolished the impedance difference between the Arr-HSC and control cells suggesting that the effect of arresten on promotion of HSC-3 cell-cell contacts and cell spreading is at least partly mediated by α1β1 integrin. Collectively, our data suggest novel roles for arresten in the regulation of oral squamous carcinoma cell proliferation, survival, motility and invasion through the modulation of cell differentiation state and integrin signaling.

Indexed as

Angiogenesis InhibitorsAnimalsAntibodies, BlockingApoptosisCadherinsCarcinoma, Squamous CellCell AdhesionCell CommunicationCell Line, TumorCell MovementCell ProliferationCollagenCollagen Type IVElectric ImpedanceEpitheliumHumansAngiogenesis InhibitorsAntibodies, BlockingCadherinsCOL4A1 protein, humanCollagenCollagen Type IVIntegrin alpha1beta1

Identifiers

PMID23227231
PMCPMC3515547
OpenAlexW1963781690

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.