Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (830 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Ubiquitous macromolecules associated with the cell surface and extracellular matrix of a wide range of cells of vertebrate and invertebrate tissues. They are essential cofactors in cell-matrix adhesion processes, in cell-cell recognition systems, and in receptor-growth factor interactions. (From Cancer Metastasis Rev 1996; 15(2): 177-86; Hepatology 1996; 24(3): 524-32)
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Proteoglycans, Heparan Sulfate; Sulfate Proteoglycans, Heparan; Heparan Sulfate Proteoglycan; Proteoglycan, Heparan Sulfate; HSPG; Proteoheparan Sulfate.
Where it fits in the MeSH classification
- Broader topics
- Proteoglycans; Heparan Sulfate
- Narrower topics
- Glypicans; Syndecans
Research landscape
PubMed indexes 8,040 records tagged with the MeSH heading “Heparan Sulfate Proteoglycans” (counts retrieved 2026-10-31). 1,727 of them (21.5%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 2,757 records.
Reviews account for 876 records (10.9%) and meta-analyses for 37. Randomized controlled trials number 69 (0.9%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 1,319 |
| 2000-2009 | 2,237 |
| 2010-2019 | 2,757 |
| 2020 onward | 1,727 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 876 | 10.9% |
| Meta-analyses | 37 | 0.5% |
| Randomized controlled trials | 69 | 0.9% |
Method: PubMed query "Heparan Sulfate Proteoglycans"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin | 2021 | Research article Design not recorded in structured metadata | 269 | cc by PMID 34325726 · DOI · PMC8323212 |
| The in vitro antiviral activity of lactoferrin against common human coronaviruses and SARS-CoV-2 is mediated by targeting the heparan sulfate co-receptor | 2021 | Research article Design not recorded in structured metadata | 159 | cc by PMID 33560940 · DOI · PMC7919907 |
| Structural basis for FGF hormone signalling | 2023 | Research article Design not recorded in structured metadata | 116 | cc by PMID 37286607 · DOI · PMC10284700 |
| Cancer-Associated Fibroblast-Derived Sphingosine-1-Phosphate Activates a MALL-SDC4 Axis to Facilitate Perineural Invasion in Pancreatic Cancer | 2026 | Research article Design not recorded in structured metadata | 0 | cc by PMID 42017444 · DOI · PMC13335594 |
IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Although chimeric antigen receptor (CAR)-engineered T cells have shown great success in the treatment of B cell malignancies, this strategy has limited efficacy in patients with solid tumors.
- Closing excerpt
- term=NCT03198546&draw=2&rank=1.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (215 words)
Although chimeric antigen receptor (CAR)-engineered T cells have shown great success in the treatment of B cell malignancies, this strategy has limited efficacy in patients with solid tumors. In mouse CAR-T cells, IL-7 and CCL19 expression have been demonstrated to improve T cell infiltration and CAR-T cell survival in mouse tumors. Therefore, in the current study, we engineered human CAR-T cells to secrete human IL-7 and CCL19 (7 × 19) and found that these 7 × 19 CAR-T cells showed enhanced capacities of expansion and migration in vitro. Furthermore, 7 × 19 CAR-T cells showed superior tumor suppression ability compared to conventional CAR-T cells in xenografts of hepatocellular carcinoma (HCC) cell lines, primary HCC tissue samples and pancreatic carcinoma (PC) cell lines. We then initiated a phase 1 clinical trial in advanced HCC/PC/ovarian carcinoma (OC) patients with glypican-3 (GPC3) or mesothelin (MSLN) expression. In a patient with advanced HCC, anti-GPC3-7 × 19 CAR-T treatment resulted in complete tumor disappearance 30 days post intratumor injection. In a patient with advanced PC, anti-MSLN-7 × 19 CAR-T treatment resulted in almost complete tumor disappearance 240 days post-intravenous infusion. Our results demonstrated that the incorporation of 7 × 19 into CAR-T cells significantly enhanced the antitumor activity against human solid tumor. Trial registration: NCT03198546. Registered 26 June 2017, https://clinicaltrials.gov/ct2/show/NCT03198546?term=NCT03198546&draw=2&rank=1.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34325726 · DOI · PMC8323212
The in vitro antiviral activity of lactoferrin against common human coronaviruses and SARS-CoV-2 is mediated by targeting the heparan sulfate co-receptor [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Coronavirus disease 2019 (COVID-19) is an ongoing pandemic that lacks effective therapeutic interventions.
- Closing excerpt
- Overall, LF appears to be a promising drug candidate for COVID-19 that warrants further investigation.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (236 words)
Coronavirus disease 2019 (COVID-19) is an ongoing pandemic that lacks effective therapeutic interventions. SARS-CoV-2 infects ACE2-expressing cells and gains cell entry through either direct plasma membrane fusion or endocytosis. Recent studies have shown that in addition to ACE2, heparan sulfate proteoglycans (HSPGs) also play an important role in SARS-CoV-2 cell attachment by serving as an attachment factor. Binding of viral spike protein to HSPGs leads to the enrichment of local concentration for the subsequent specific binding with ACE2. We therefore hypothesize that blocking the interactions between viral spike protein and the HSPGs will lead to inhibition of viral replication. In this study, we report our findings of the broad-spectrum antiviral activity and the mechanism of action of lactoferrin (LF) against multiple common human coronaviruses as well as SARS-CoV-2. Our study has shown that LF has broad-spectrum antiviral activity against SARS-CoV-2, HCoV-OC43, HCoV-NL63, and HCoV-229E in cell culture, and bovine lactoferrin (BLF) is more potent than human lactoferrin. Mechanistic studies revealed that BLF binds to HSPGs, thereby blocking viral attachment to the host cell. The antiviral activity of BLF can be antagonized by the HSPG mimetic heparin. Combination therapy experiment showed that the antiviral activity of LF is synergistic with remdesivir in cell culture. Molecular modelling suggests that the N-terminal positively charged region in BLF (residues 17-41) confers the binding to HSPGs. Overall, LF appears to be a promising drug candidate for COVID-19 that warrants further investigation.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33560940 · DOI · PMC7919907
Structural basis for FGF hormone signalling [3]
Abstract reading summary — source excerpts
- Opening excerpt
- α/βKlotho coreceptors simultaneously engage fibroblast growth factor (FGF) hormones (FGF19, FGF21 and FGF23)1,2 and their cognate cell-surface FGF receptors (FGFR1-4) thereby stabilizing the endocrine FGF-FGFR complex3-6.
- Closing excerpt
- Our structural and biochemical data overturn the current symmetric FGFR dimerization paradigm and provide blueprints for rational discovery of modulators of FGF signalling2 as therapeutics for human metabolic diseases and cancer.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (196 words)
α/βKlotho coreceptors simultaneously engage fibroblast growth factor (FGF) hormones (FGF19, FGF21 and FGF23)1,2 and their cognate cell-surface FGF receptors (FGFR1-4) thereby stabilizing the endocrine FGF-FGFR complex3-6. However, these hormones still require heparan sulfate (HS) proteoglycan as an additional coreceptor to induce FGFR dimerization/activation and hence elicit their essential metabolic activities6. To reveal the molecular mechanism underpinning the coreceptor role of HS, we solved cryo-electron microscopy structures of three distinct 1:2:1:1 FGF23-FGFR-αKlotho-HS quaternary complexes featuring the 'c' splice isoforms of FGFR1 (FGFR1c), FGFR3 (FGFR3c) or FGFR4 as the receptor component. These structures, supported by cell-based receptor complementation and heterodimerization experiments, reveal that a single HS chain enables FGF23 and its primary FGFR within a 1:1:1 FGF23-FGFR-αKlotho ternary complex to jointly recruit a lone secondary FGFR molecule leading to asymmetric receptor dimerization and activation. However, αKlotho does not directly participate in recruiting the secondary receptor/dimerization. We also show that the asymmetric mode of receptor dimerization is applicable to paracrine FGFs that signal solely in an HS-dependent fashion. Our structural and biochemical data overturn the current symmetric FGFR dimerization paradigm and provide blueprints for rational discovery of modulators of FGF signalling2 as therapeutics for human metabolic diseases and cancer.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 37286607 · DOI · PMC10284700
Cancer-Associated Fibroblast-Derived Sphingosine-1-Phosphate Activates a MALL-SDC4 Axis to Facilitate Perineural Invasion in Pancreatic Cancer [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Pancreatic ductal adenocarcinoma (PDAC) frequently exhibits perineural invasion (PNI), a clinicopathologic feature strongly associated with local recurrence and poor survival, yet lacking effective targeted interventions.
- Closing excerpt
- These findings uncover a metabolite-driven MALL-SDC4 program connecting stromal metabolism to neural invasion, and identify promising therapeutic targets for PDAC.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (183 words)
Pancreatic ductal adenocarcinoma (PDAC) frequently exhibits perineural invasion (PNI), a clinicopathologic feature strongly associated with local recurrence and poor survival, yet lacking effective targeted interventions. By integrating patient cohorts with single-cell and bulk transcriptomics, multiplex immunofluorescence, and functional assays, this study defines a stromal-tumor signaling axis facilitating neural invasion. Cancer-associated fibroblasts (CAFs), particularly a myofibroblastic CAF-enriched population, upregulate sphingosine kinase 1 (SPHK1) and increase secretion of sphingosine-1-phosphate (S1P), which activates sphingosine-1-phosphate receptor 3 (S1PR3)/JNK/JUN signaling to transcriptionally induce MAL-like protein (MALL) in cancer cells. MALL binds to syndecan-4 (SDC4) and promotes its recycling to the plasma membrane, thereby increasing surface SDC4 abundance. This MALL-SDC4 program promotes RhoA/phosphorylated myosin light chain 2 (p-MLC2)-dependent amoeboid motility and sensitizes cancer cells to Schwann cell-derived pleiotrophin, strengthening directed neural invasion. Disruption of the axis through SPHK1 knockdown in CAFs, genetic perturbation of MALL or SDC4 in cancer cells, or adeno-associated virus-mediated SPHK1 or SDC4 knockdown in KPC (KrasLSL-G12D/+; Trp53LSL-R172H/+; Pdx1-Cre) mice significantly reduces PNI and tumor burden. These findings uncover a metabolite-driven MALL-SDC4 program connecting stromal metabolism to neural invasion, and identify promising therapeutic targets for PDAC.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42017444 · DOI · PMC13335594
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Heparan sulfate proteoglycans [5]
- Research article Functions of heparan sulfate proteoglycans in cell signaling during development [6]
- Research article Glypicans [7]
- Research article The nature and biology of basement membranes [8]
- Research article Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein E [9]
- Research article Heparan sulfate proteoglycan as a cell-surface endocytosis receptor [10]
References
- Pang N, Shi J, Qin L, Chen A, Tang Y, Yang H, et al.. IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin. . 2021. PMID 34325726 · DOI · PMC8323212
- Hu Y, Meng X, Zhang F, Xiang Y, Wang J. The in vitro antiviral activity of lactoferrin against common human coronaviruses and SARS-CoV-2 is mediated by targeting the heparan sulfate co-receptor. . 2021. PMID 33560940 · DOI · PMC7919907
- Chen L, Fu L, Sun J, Huang Z, Fang M, Zinkle A, et al.. Structural basis for FGF hormone signalling. . 2023. PMID 37286607 · DOI · PMC10284700
- Peng W, Cao M, Huang H, Bai S, Liu L, Liang J, et al.. Cancer-Associated Fibroblast-Derived Sphingosine-1-Phosphate Activates a MALL-SDC4 Axis to Facilitate Perineural Invasion in Pancreatic Cancer. . 2026. PMID 42017444 · DOI · PMC13335594
- Sarrazin S, Lamanna WC, Esko JD. Heparan sulfate proteoglycans. Cold Spring Harb Perspect Biol. 2011. PMID 21690215 · DOI · PMC3119907
- Lin X. Functions of heparan sulfate proteoglycans in cell signaling during development. Development. 2004. PMID 15563523 · DOI
- Filmus J, Capurro M, Rast J. Glypicans. Genome Biol. 2008. PMID 18505598 · DOI · PMC2441458
- Pozzi A, Yurchenco PD, Iozzo RV. The nature and biology of basement membranes. Matrix Biol. 2017. PMID 28040522 · DOI · PMC5387862
- Mahley RW, Ji ZS. Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein E. J Lipid Res. 1999. PMID 9869645 · DOI
- Christianson HC, Belting M. Heparan sulfate proteoglycan as a cell-surface endocytosis receptor. Matrix Biol. 2014. PMID 24145152 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.