ArticleOncogene2022
Fibroblast-derived prolargin is a tumor suppressor in hepatocellular carcinoma.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 34 citations in OpenAlex.
- Reversible homodimerization of a small leucine-rich proteoglycan PRELP modulates the interactions with TGFβ1 and IGFI-R.The Journal of biological chemistry · 2026Article
- Protective effects of PRELP protein in a mouse model of pulmonary fibrosis.Respiratory research · 2026Article
- Allogeneic Immune Cell Perfusion Inhibits the Growth of Vascularized 3D In Vitro Tumor Models, Induces Vascular Regression and Desmoplasia, but Promotes Tumor Cell Invasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Clinical applications of immunogenomics in hepatocellular carcinoma.Clinical and molecular hepatology · 2026Review
- Pleiotropic mechanisms of cancer-associated fibroblast-mediated resistance in hepatocellular carcinoma: emerging therapeutic vulnerabilities and targeting strategies.Cancer gene therapy · 2026Review
- Sorafenib nanomedicine in HCC: nano-bio interactions and combination therapies.Journal of nanobiotechnology · 2026Review
- PRELP-associated transcriptomic remodeling links alternative splicing and immune checkpoint blockade outcome in melanoma.Frontiers in immunology · 2026Article
- Single-cell insights into hepatic fibroblasts and stellate cells: heterogeneity in matrix remodelling in development, health, and disease.Npj gut and liver · 2026Review
- Cancer-associated fibroblasts, clinicopathological characteristics and prognosis of liver cancer: A systematic review and meta-analysis based on real-world research.World journal of gastrointestinal oncology · 2025Article
- Impact of pancreatic proenzymes on pancreatic ductal adenocarcinoma associated fibroblasts.Scientific reports · 2025Article
- PRELP functions via multiple interactions with intrinsically weak affinity relying on ECM anchoring and remodeling.Scientific reports · 2025Article
- circCEP70 encoded protein inhibits the progression of hepatocellular carcinoma.Cellular and molecular life sciences : CMLS · 2025Article
- Review
- Cancer-associated fibroblasts in hepatocellular carcinoma: origins, heterogeneity, and therapeutic implications.Frontiers in immunology · 2025Review
- CAFs vs. TECs: when blood feuds fuel cancer progression, dissemination and therapeutic resistance.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Cancer-Associated Fibroblast Heterogeneity in Malignancy with Focus on Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2024Review
- Article
- Friend or foe? The elusive role of hepatic stellate cells in liver cancer.Nature reviews. Gastroenterology & hepatology · 2023Review
- Correlation of the tumor escape phenotype with loss of PRELP expression in melanoma.Journal of translational medicine · 2023Article
- Immune System and Hepatocellular Carcinoma (HCC): New Insights into HCC Progression.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer-associated fibroblasts (CAF) are important constituents of the tumor microenvironment (TME) and are major drivers of tumorigenesis. Yet, therapies aiming at eliminating CAF have failed to cure patients. This setback has raised questions regarding whether CAF exclusively favour cancer progression, or if they may also assume tumor-suppressor functions. In the present study, we used proteomics and single cell RNA-sequencing analysis to examine the CAF landscape in hepatocellular carcinoma (HCC). We thereby unveil three major CAF populations in HCC, one of which specifically expressing the prolargin protein. This CAF subpopulation (further termed as CAF_Port) shared a strong transcriptomic signature with portal liver fibroblasts. We further show that CAF_Port deposit prolargin in the TME and that its levels are lower in tumors as compared to the peritumoral region. Mechanistically, aggressive cancer cells degraded prolargin using matrix metalloprotease activity. Survival analysis of 188 patients revealed that high prolargin protein levels correlate with good patient outcome (HR = 0.37; p = 0.01). In vivo, co-injection of cancer cells with fibroblasts silenced for prolargin, led to faster tumor development (5-fold; p = 0.01), mainly due to stronger angiogenesis. Using protein-protein interaction study and structural modelling, we further demonstrate that prolargin binds and inhibits the activity of several pro-agiogenic proteins, including hepatocyte and fibroblast growth factors. In conclusion, prolargin is angiogenesis modulator and CAF-derived tumor suppressor in HCC. Stabilizing prolargin levels in the CAF_Port subpopulation may revert their tumor-antagonizing properties, warranting exploration in further pre-clinical studies.
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Registered trials
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.