ArticleThe Journal of clinical investigation2021
Tumor restriction by type I collagen opposes tumor-promoting effects of cancer-associated fibroblasts.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 250 papers.
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Who cites it
250 citing papers in PubMed, 346 citations in OpenAlex.
- Gemcitabine and nab-paclitaxel with or without the VDR agonist paricalcitol for metastatic pancreatic cancer: a randomized, multiarm, run-in phase trial.Nature cancer · 2026Trial
- Development and validation of a radiomics model of magnetic resonance for predicting liver metastasis in resectable pancreatic ductal adenocarcinoma patients.Radiation oncology (London, England) · 2023Trial
- Before the seeds arrive: pre-metastatic niche orchestration in bladder cancer.Cancer metastasis reviews · 2026Review
- An integrated spatially defined roadmap of normal and cancer-associated colon fibroblasts.Molecular systems biology · 2026Article
- Extracellular Matrix Remodeling in Tumors: Forces Beyond Fibroblasts.Cancer research · 2026Article
- Comparative Analysis of Primary and Liver Fibroblasts Reveals MET as a Potent Target in Pancreatic Cancer Metastasis.Cellular and molecular gastroenterology and hepatology · 2026Article
- Fibronectin matrix remodelling modulates the active nematic dynamics of cancer-associated fibroblasts.Nature materials · 2026Article
- Article
- Location matters: Spatial-dependent effects of myofibroblasts modulate survival in breast cancer.iScience · 2026Article
- Heterogeneity characterization and therapeutic marker discovery of endometrial carcinoma using GeoMXT™ digital spatial profiling.Journal of translational medicine · 2026Article
- Molecular phenotypes and spatial archetypes: A new framework for cancer-associated fibroblasts.Cancer cell · 2026Review
- Fibroblasts: a diverse population of cells balancing homeostasis, wound healing, regeneration, inflammation, fibrosis, and cancer across organs.JCI insight · 2026Review
- TUFT1 stabilizes TGF-β receptor II protein and facilitates activation of hepatic stellate cells into metastasis-promoting myofibroblasts.Cell death and differentiation · 2026Article
- Role of the stromal and immune microenvironment in intrahepatic cholangiocarcinoma.JHEP reports : innovation in hepatology · 2026Review
- Matrix stiffness drives squamous cell carcinoma progression via a Piezo1-mediated mechanotransduction feedback loop.Journal of advanced research · 2026Article
- From steatosis to metastasis: microenvironmental reprogramming of the liver in metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Article
- Arp2/3 complex and β1 integrin drive an invasive front through extracellular matrix adaptation in pancreatic cancer.International journal of cancer · 2026Article
- Heterogeneity of Cancer-Associated Fibroblasts and Precision Targeting Strategies for Cancer Therapy.Thoracic cancer · 2026Review
- Glutamine-dependent changes in fibroblast-derived extracellular matrix dictate cancer cell behavior.Matrix biology : journal of the International Society for Matrix Biology · 2026Article
190 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 10 institutions in 3 countries.
Funding
Abstract
Cancer-associated fibroblasts (CAF) may exert tumor-promoting and tumor-suppressive functions, but the mechanisms underlying these opposing effects remain elusive. Here, we sought to understand these potentially opposing functions by interrogating functional relationships among CAF subtypes, their mediators, desmoplasia, and tumor growth in a wide range of tumor types metastasizing to the liver, the most common organ site for metastasis. Depletion of hepatic stellate cells (HSC), which represented the main source of CAF in mice and patients in our study, or depletion of all CAF decreased tumor growth and mortality in desmoplastic colorectal and pancreatic metastasis but not in nondesmoplastic metastatic tumors. Single-cell RNA-Seq in conjunction with CellPhoneDB ligand-receptor analysis, as well as studies in immune cell-depleted and HSC-selective knockout mice, uncovered direct CAF-tumor interactions as a tumor-promoting mechanism, mediated by myofibroblastic CAF-secreted (myCAF-secreted) hyaluronan and inflammatory CAF-secreted (iCAF-secreted) HGF. These effects were opposed by myCAF-expressed type I collagen, which suppressed tumor growth by mechanically restraining tumor spread, overriding its own stiffness-induced mechanosignals. In summary, mechanical restriction by type I collagen opposes the overall tumor-promoting effects of CAF, thus providing a mechanistic explanation for their dual functions in cancer. Therapeutic targeting of tumor-promoting CAF mediators while preserving type I collagen may convert CAF from tumor promoting to tumor restricting.
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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.