ArticleOncogene2014
Osteopontin signaling upregulates cyclooxygenase-2 expression in tumor-associated macrophages leading to enhanced angiogenesis and melanoma growth via α9β1 integrin.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 86 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 147 citations in OpenAlex.
- Pooled it
- Pre-diagnostic metabolites in peripheral blood of Langerhans cell histiocytosis children with posterior pituitary involvement.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Osteopontin mediates acquired resistance to hypoxia-inducing antiangiogenics and promotes anti-PD-L1 refractoriness in breast cancer models.The Journal of clinical investigation · 2026Article
- Uncovering the Intricate and Heterogeneous Cellular Microenvironment of Cutaneous Melanoma.Medicina (Kaunas, Lithuania) · 2026Review
- The crucial role of SPP1 in osteoporosis, osteoarthritis, and cancer.Pharmaceutical science advances · 2025Review
- Role of Matricellular Proteins in Endothelial Cell Inflammation and Atherosclerosis.Antioxidants (Basel, Switzerland) · 2025Review
- Role of osteopontin in cancer: From pathogenesis to therapeutics (Review).Oncology reports · 2025Review
- Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications.Molecular cancer · 2025Review
- Tumor-associated macrophages remodel the suppressive tumor immune microenvironment and targeted therapy for immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Review
- Targeting tumor-associated macrophages: Novel insights into immunotherapy of skin cancer.Journal of advanced research · 2025Review
- Targeted SPP1 Inhibition of Tumor-Associated Myeloid Cells Effectively Decreases Tumor Sizes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Lipid metabolic rewiring in glioma‑associated microglia/macrophages (Review).International journal of molecular medicine · 2024Review
- Osteopontin Regulates Treg Cell Stability and Function with Implications for Anti-Tumor Immunity and Autoimmunity.Cancers · 2024Article
- Identification of diagnostic biomarkers and immune cell infiltration in tongue squamous cell carcinoma using bioinformatic approaches.European journal of medical research · 2024Article
- Osteopontin: A Key Multifaceted Regulator in Tumor Progression and Immunomodulation.Biomedicines · 2024Review
- Determinants of resistance and response to melanoma therapy.Nature cancer · 2024Review
- SPP1Cancer gene therapy · 2024Article
- Article
- Impaired fracture healing is associated with callus chondro-osseous junction abnormalities in periostin-null and osteopontin-null mice.Experimental biology and medicine (Maywood, N.J.) · 2024Article
- Role of osteopontin in cancer development and treatment.Heliyon · 2023Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor-associated macrophages (TAMs) have multifaceted roles in tumor development, particularly linked with tumor angiogenesis and invasion, but the molecular mechanism underlying this association remains unclear. In this study, we report that lack of osteopontin (OPN) suppresses melanoma growth in opn(-/-) mice and macrophages are the crucial component responsible for OPN-regulated melanoma growth. In tumor microenvironment, OPN activates macrophages and influences angiogenesis by enhancing cyclooxygenase-2 (COX-2)-dependent prostaglandin E2 (PGE2) production in an autocrine manner. Furthermore, we identify α9β1 integrin as a functional receptor for OPN that mediates its effect and activates ERK and p38 signaling, which ultimately leads to COX-2 expression in macrophages. The major role played by OPN and PGE2 in angiogenesis are further amplified by upregulation of MMP-9. OPN-activated macrophages promote the migration of endothelial and cancer cells via PGE2. These findings provide evidence that TAMs serve as source of key components such as OPN and COX-2-derived PGE2 and MMP-9 in melanoma microenvironment. Clinical specimens analyses revealed that increased infiltration of OPN-positive TAMs correlate with melanoma growth and angiogenesis. These data provide compelling evidence that OPN and COX-2 expressing macrophages are obligatory factors in melanoma growth. We conclude that OPN signaling is involved in macrophage recruitment into tumor, and our results emphasize the potential role of macrophage in modulation of tumor microenvironment via secretion of OPN, PGE2 and MMP-9, which trigger angiogenesis and melanoma growth. Thus, blockade of OPN and its regulated signaling network provides unique strategy to eradicate melanoma by manipulating TAMs.
Indexed as
Identifiers
What OpenQuestion holds
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.