Evidence map›Paper›PMID 33927256›Full record

ArticleScientific reports2021

Inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line.

Sukhneeraj P Kaur, Arti Verma, Hee K Lee, Lillie M Barnett, Payaningal R Somanath, Brian S Cummings

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 37% 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

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. 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

6 authors at 3 institutions in 1 country.

Sukhneeraj P KaurDepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, 450 College of Pharmacy South, Athens, GA, 30607, USA.
Arti VermaClinical and Experimental Therapeutics, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA, USA.
Hee K LeeMedical College of Georgia, Augusta University, Augusta, GA, USA.
Lillie M BarnettInterdisciplinary Toxicology Program, University of Georgia, Athens, GA, USA.
Payaningal R SomanathClinical and Experimental Therapeutics, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA, USA.
Brian S CummingsDepartment of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, 450 College of Pharmacy South, Athens, GA, 30607, USA. briansc@uga.edu.
University of Georgia · USCharlie Norwood VA Medical Center · USAugusta University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer-associated fibroblasts (CAFs) are the most abundant stromal cell type in the tumor microenvironment. CAFs orchestrate tumor-stromal interactions, and contribute to cancer cell growth, metastasis, extracellular matrix (ECM) remodeling, angiogenesis, immunomodulation, and chemoresistance. However, CAFs have not been successfully targeted for the treatment of cancer. The current study elucidates the significance of glypican-1 (GPC-1), a heparan sulfate proteoglycan, in regulating the activation of human bone marrow-derived stromal cells (BSCs) of fibroblast lineage (HS-5). GPC-1 inhibition changed HS-5 cellular and nuclear morphology, and increased cell migration and contractility. GPC-1 inhibition also increased pro-inflammatory signaling and CAF marker expression. GPC-1 induced an activated fibroblast phenotype when HS-5 cells were exposed to prostate cancer cell conditioned media (CCM). Further, treatment of human bone-derived prostate cancer cells (PC-3) with CCM from HS-5 cells exhibiting GPC-1 loss increased prostate cancer cell aggressiveness. Finally, GPC-1 was expressed in mouse tibia bone cells and present during bone loss induced by mouse prostate cancer cells in a murine prostate cancer bone model. These data demonstrate that GPC-1 partially regulates the intrinsic and extrinsic phenotype of human BSCs and transformation into activated fibroblasts, identify novel functions of GPC-1, and suggest that GPC-1 expression in BSCs exerts inhibitory paracrine effects on the prostate cancer cells. This supports the hypothesis that GPC-1 may be a novel pharmacological target for developing anti-CAF therapeutics to control cancer.

Indexed as

AnimalsCancer-Associated FibroblastsCell MovementFibroblastsGlypicansHumansMaleMesenchymal Stem CellsMiceMice, Inbred C57BLPhenotypeProstatic NeoplasmsTumor MicroenvironmentGlypicans

Identifiers

PMID33927256
PMCPMC8084937
OpenAlexW3159554448

What OpenQuestion holds

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LicenceCC BY
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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.