ArticleOncogene2024
DDR2-regulated arginase activity in ovarian cancer-associated fibroblasts promotes collagen production and tumor progression.
Article in Oncogene, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Collagenase-mediated extracellular matrix targeting for enhanced drug penetration and therapeutic efficacy in nanoscale delivery systems for cancer therapy.Journal of nanobiotechnology · 2025Pooled it
- Colorectal Cancer Liver Metastasis-Associated Ferroptosis-Related Genes Modulate Lipid Peroxidation in Colorectal Cancer Cells.Molecular carcinogenesis · 2026Article
- Multi-omics analysis of arginine metabolism in ovarian cancer: A prognostic signature and GTF2F2-driven stromal remodeling.Translational oncology · 2026Article
- Amino Acids as Targets for Immunotherapy against Solid Tumors.Cell biochemistry and biophysics · 2026Review
- Rethinking ovarian cancer III: the past decade and future directions.Nature reviews. Cancer · 2026Review
- Metabolic crosstalk among cancer-associated fibroblasts, adipocytes and immune cells as an immunosuppressive tumor microenvironment driver.Experimental & molecular medicine · 2026Review
- Cancer-associated fibroblasts as a critical driver in tumor metastasis: The mechanisms and future perspectives.iScience · 2026Review
- ARG1-polyamine axis: cell-type-specific functions in disease pathogenesis and therapeutic targeting.Frontiers in immunology · 2026Review
- Amino acids metabolism: a potential target for cancer treatment.Molecular cancer · 2025Review
- The Application of Nanomaterials in Breast Cancer.Pharmaceutics · 2025Review
- DDR2 Confers Ferroptosis Resistance to Cancer-Associated Fibroblasts and Attenuates PARPi Sensitivity of Ovarian Tumor Cells.Molecular cancer research : MCR · 2025Article
- Insights into the relevance of targeting fibroblasts to control cancer.Cell reports. Medicine · 2025Review
- Discoidin domain receptor tyrosine kinase 2: A new perspective on microenvironment remodeling and targeted therapy of solid tumors (Review).Oncology letters · 2025Review
- Transcriptomics combined withTranslational cancer research · 2025Article
- Conjoint analysis of single-cell sequencing and high-throughput virtual screening regarding DDR2 in osteoarthritis disease models.European journal of medical research · 2025Article
- Autophagy disruption primes CAR-T cell metabolism for sustained rejection of ovarian tumors.bioRxiv : the preprint server for biology · 2025Article
- The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025Review
- Discoidin Domain Receptors in Tumor Biology and Immunology: Progression and Challenge.Biomolecules · 2025Review
- The fibroinflammatory response in cancer.Nature reviews. Cancer · 2025Review
- Metabolomic reprogramming of the tumor microenvironment by dual arginase inhibitor OATD-02 boosts anticancer immunity.Scientific reports · 2025Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Ovarian cancer has poor survival outcomes particularly for advanced stage, metastatic disease. Metastasis is promoted by interactions of stromal cells, such as cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME), with tumor cells. CAFs play a key role in tumor progression by remodeling the TME and extracellular matrix (ECM) to result in a more permissive environment for tumor progression. It has been shown that fibroblasts, in particular myofibroblasts, utilize metabolism to support ECM remodeling. However, the intricate mechanisms by which CAFs support collagen production and tumor progression are poorly understood. In this study, we show that the fibrillar collagen receptor, Discoidin Domain Receptor 2 (DDR2), promotes collagen production in human and mouse omental CAFs through arginase activity. CAFs with high DDR2 or arginase promote tumor colonization in the omentum. In addition, DDR2-depleted CAFs had decreased ornithine levels leading to decreased collagen production and polyamine levels compared to WT control CAFs. Tumor cell invasion was decreased in the presence CAF conditioned media (CM) depleted of DDR2 or arginase-1, and this invasion defect was rescued in the presence of CM from DDR2-depleted CAFs that constitutively overexpressed arginase-1. Similarly, the addition of exogenous polyamines to CM from DDR2-depleted CAFs led to increased tumor cell invasion. We detected SNAI1 protein at the promoter region of the arginase-1 gene, and DDR2-depleted CAFs had decreased levels of SNAI1 protein at the arginase-1 promoter region. Furthermore, high stromal arginase-1 expression correlated with poor survival in ovarian cancer patients. These findings highlight how DDR2 regulates collagen production by CAFs in the tumor microenvironment by controlling the transcription of arginase-1, and CAFs are a major source of arginase activity and L-arginine metabolites in ovarian cancer models.
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Registered trials
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