Evidence map›Paper›PMID 33592387›Full record

ArticleBiomaterials2021

Elucidating cancer-vascular paracrine signaling using a human organotypic breast cancer cell extravasation model.

Mouhita Humayun, Jose M Ayuso, Raven A Brenneke, María Virumbrales-Muñoz, Karina Lugo-Cintrón, Sheena Kerr, Suzanne M Ponik, David J Beebe

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomaterials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
2.9field-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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Microphysiological systems for metastasis research: a stepwise approach.Cellular oncology (Dordrecht, Netherlands) · 2025
    Review
  5. Review
  6. The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025
    Review
  7. Article
  8. Review
  9. Article
  10. Multi-stage mechanisms of tumor metastasis and therapeutic strategies.Signal transduction and targeted therapy · 2024
    Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Cancer 3D Models for Metallodrug Preclinical Testing.International journal of molecular sciences · 2023
    Review
  18. 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

8 authors at 2 institutions in 1 country.

Mouhita HumayunDepartment of Biomedical Engineering, University of Wisconsin- Madison, 1415 Engineering Drive, Madison, WI, 53706, USA; The University of Wisconsin Carbone Cancer Center, University of Wisconsin- Madison, WIMR I Room 6028 - 1111 Highland Ave, Madison, WI, 53705, USA. Electronic address: humayun@wisc.edu.
Jose M AyusoDepartment of Biomedical Engineering, University of Wisconsin- Madison, 1415 Engineering Drive, Madison, WI, 53706, USA; The University of Wisconsin Carbone Cancer Center, University of Wisconsin- Madison, WIMR I Room 6028 - 1111 Highland Ave, Madison, WI, 53705, USA.
Raven A BrennekeDepartment of Biomedical Engineering, University of Wisconsin- Madison, 1415 Engineering Drive, Madison, WI, 53706, USA.
María Virumbrales-MuñozDepartment of Biomedical Engineering, University of Wisconsin- Madison, 1415 Engineering Drive, Madison, WI, 53706, USA; The University of Wisconsin Carbone Cancer Center, University of Wisconsin- Madison, WIMR I Room 6028 - 1111 Highland Ave, Madison, WI, 53705, USA.
Karina Lugo-CintrónDepartment of Biomedical Engineering, University of Wisconsin- Madison, 1415 Engineering Drive, Madison, WI, 53706, USA; The University of Wisconsin Carbone Cancer Center, University of Wisconsin- Madison, WIMR I Room 6028 - 1111 Highland Ave, Madison, WI, 53705, USA.
Sheena KerrThe University of Wisconsin Carbone Cancer Center, University of Wisconsin- Madison, WIMR I Room 6028 - 1111 Highland Ave, Madison, WI, 53705, USA; Department of Pathology & Laboratory Medicine, University of Wisconsin- Madison, 1685 Highland Avenue, Madison, WI, 53705, USA.
Suzanne M PonikThe University of Wisconsin Carbone Cancer Center, University of Wisconsin- Madison, WIMR I Room 6028 - 1111 Highland Ave, Madison, WI, 53705, USA; Department of Cell and Regenerative Biology, University of Wisconsin- Madison, 1300 University Ave, Madison, WI, 53706, USA.
David J BeebeDepartment of Biomedical Engineering, University of Wisconsin- Madison, 1415 Engineering Drive, Madison, WI, 53706, USA; The University of Wisconsin Carbone Cancer Center, University of Wisconsin- Madison, WIMR I Room 6028 - 1111 Highland Ave, Madison, WI, 53705, USA; Department of Pathology & Laboratory Medicine, University of Wisconsin- Madison, 1685 Highland Avenue, Madison, WI, 53705, USA. Electronic address: djbeebe@wisc.edu.
University of Wisconsin–Madison · USUniversity of Wisconsin System · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Christian Capitini · 1985 to 2026
$142.6M
An automated high-throughput tissue model for screening metastatic effectorsR01CA186134 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI BEEBE, DAVID J · 2015 to 2019
$3.1M
Targeting cancer-stroma interactions in breast cancer metastasis using organotypic modelingF31CA247248 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI HUMAYUN, MOUHITA · 2019 to 2021
$67k
NCI NIH HHS F31 CA247248NCI NIH HHS P30 CA014520NCI NIH HHS R01 CA186134
6 · The paper itself

Abstract

In cancer metastasis, extravasation refers to the process where tumor cells exit the bloodstream by crossing the endothelium and invade the surrounding tissue. Tumor cells engage in complex crosstalk with other active players such as the endothelium leading to changes in functional behavior that exert pro-extravasation effects. Most in vitro studies to date have only focused on the independent effects of molecular targets on the functional changes of cancer cell extravasation behavior. However, singular targets cannot combat complex interactions involved in tumor cell extravasation that affects multiple cell types and signaling pathways. In this study, we employ an organotypic microfluidic model of human vasculature to investigate the independent and combined role of multiple upregulated secreted factors resulting from cancer-vascular interactions during cancer cell extravasation. The device consists of a tubular endothelial vessel generated from induced pluripotent stem cell derived endothelial cells within a collagen-fibrinogen matrix with breast cancer cells injected through and cultured along the lumen of the vessel. Our system identified cancer-vascular crosstalk, involving invasive breast cancer cells, that results in increased levels of secreted IL-6, IL-8, and MMP-3. Our model also showed that upregulation of these secreted factors correlates with invasive/metastatic potential of breast cancer cells. We also used therapeutic inhibitors to assess the independent and combined role of multiple signaling factors on the overall changes in functional behavior of both the cancer cells and the endothelium that promote extravasation. Taken together, these results demonstrate the potential of our organotypic model in elucidating mechanisms through which cancer-vascular interactions can promote extravasation, and in conducting functional assessment of therapeutic drugs that prevent extravasation in cancer metastasis.

Indexed as

Breast NeoplasmsEndothelial CellsCell Line, TumorHumansMicrofluidicsParacrine CommunicationCancer cell extravasationEndothelial vesselsInduced pluripotent stem cell-derived endothelial cellsMicrofluidic in vitro modelTherapeutic drug testing platform

Identifiers

PMID33592387
PMCPMC9703973
OpenAlexW3126494168

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.