ArticleThe Journal of biological chemistry2015
Direct Melanoma Cell Contact Induces Stromal Cell Autocrine Prostaglandin E2-EP4 Receptor Signaling That Drives Tumor Growth, Angiogenesis, and Metastasis.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
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.
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Who cites it
21 citing papers in PubMed, 45 citations in OpenAlex.
- Time-Resolved Metabolomics Reveals Distinct, Cell- and Variety-Dependent Profiles of Prostanoids in Melanoma Cells Exposed to Fruit Extracts fromInternational journal of molecular sciences · 2026Article
- Reprogramming inflammation: Mechanisms and therapeutic targeting of eicosanoids and pro-resolving mediators.European journal of pharmacology · 2025Review
- Prostaglandin E2 Exposure Disrupts E-Cadherin/Caveolin-1-Mediated Tumor Suppression to Favor Caveolin-1-Enhanced Migration, Invasion, and Metastasis in Melanoma Models.International journal of molecular sciences · 2023Article
- Enhancement of Radiation Therapy through Blockade of the Immune Checkpoint, V-domain Ig Suppressor of T Cell Activation (VISTA), in Melanoma and Adenocarcinoma Murine Models.International journal of molecular sciences · 2023Article
- Engineered in vitro tumor models for cell-based immunotherapy.Acta biomaterialia · 2021Review
- Review
- Premetastasis.Cold Spring Harbor perspectives in medicine · 2020Review
- Lipid metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives.Cancers · 2020Review
- International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin EPharmacological reviews · 2020Article
- Cutaneous melanoma dissemination is dependent on the malignant cell properties and factors of intercellular crosstalk in the cancer microenvironment (Review).International journal of oncology · 2020Review
- [Research progress of Candida albicans on malignant transformation of oral mucosal diseases].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2020Review
- Eicosanoids in Cancer: Prostaglandin EFrontiers in pharmacology · 2020Review
- Prostaglandin E2/EP Signaling in the Tumor Microenvironment of Colorectal Cancer.International journal of molecular sciences · 2019Review
- Inhibition of COX-2, mPGES-1 and CYP4A by isoliquiritigenin blocks the angiogenic Akt signaling in glioma through ceRNA effect of miR-194-5p and lncRNA NEAT1.Journal of experimental & clinical cancer research : CR · 2019Article
- The first case of primary hypertrophic osteoarthropathy with soft tissue giant tumors caused by HPGD loss-of-function mutation.Endocrine connections · 2019Article
- Activated Fibroblast Program Orchestrates Tumor Initiation and Progression; Molecular Mechanisms and the Associated Therapeutic Strategies.International journal of molecular sciences · 2019Review
- The HU177 Collagen Epitope Controls Melanoma Cell Migration and Experimental Metastasis by a CDK5/YAP-Dependent Mechanism.The American journal of pathology · 2018Article
- The evolving relationship of wound healing and tumor stroma.JCI insight · 2018Review
- MgClExperimental and therapeutic medicine · 2017Article
- The MET/Vascular Endothelial Growth Factor Receptor (VEGFR)-targeted Tyrosine Kinase Inhibitor Also Attenuates FMS-dependent Osteoclast Differentiation and Bone Destruction Induced by Prostate Cancer.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
The stromal cells associated with tumors such as melanoma are significant determinants of tumor growth and metastasis. Using membrane-bound prostaglandin E synthase 1 (mPges1(-/-)) mice, we show that prostaglandin E2 (PGE2) production by host tissues is critical for B16 melanoma growth, angiogenesis, and metastasis to both bone and soft tissues. Concomitant studies in vitro showed that PGE2 production by fibroblasts is regulated by direct interaction with B16 cells. Autocrine activity of PGE2 further regulates the production of angiogenic factors by fibroblasts, which are key to the vascularization of both primary and metastatic tumor growth. Similarly, cell-cell interactions between B16 cells and host osteoblasts modulate mPGES-1 activity and PGE2 production by the osteoblasts. PGE2, in turn, acts to stimulate receptor activator of NF-κB ligand expression, leading to osteoclast differentiation and bone erosion. Using eicosanoid receptor antagonists, we show that PGE2 acts on osteoblasts and fibroblasts in the tumor microenvironment through the EP4 receptor. Metastatic tumor growth and vascularization in soft tissues was abrogated by an EP4 receptor antagonist. EP4-null Ptger4(-/-) mice do not support B16 melanoma growth. In vitro, an EP4 receptor antagonist modulated PGE2 effects on fibroblast production of angiogenic factors. Our data show that B16 melanoma cells directly influence host stromal cells to generate PGE2 signals governing neoangiogenesis and metastatic growth in bone via osteoclast erosive activity as well as angiogenesis in soft tissue tumors.
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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.