ArticlePloS one2016
Semaphorin 4D Promotes Skeletal Metastasis in Breast Cancer.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 44 citations in OpenAlex.
- The Neuro-Bone Axis in Metastatic Progression: Innervation, Neuro-Immune-Osteoclast Crosstalk, and Therapeutic Opportunities.Biology · 2026Review
- CeiTEA: Adaptive Hierarchy of Single Cells with Topological Entropy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- MDA-9/Syntenin in the tumor and microenvironment defines prostate cancer bone metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Semaphorins and Their Roles in Breast Cancer: Implications for Therapy Resistance.International journal of molecular sciences · 2023Review
- Soluble Sema4D cleaved from osteoclast precursors by TACE suppresses osteoblastogenesis.Journal of cellular and molecular medicine · 2023Article
- Review
- Chemokines network in bone metastasis: Vital regulators of seeding and soiling.Seminars in cancer biology · 2022Review
- Sema4D/Plexin-B1 promotes the progression of osteosarcoma cells by activating Pyk2-PI3K-AKT pathway.Journal of musculoskeletal & neuronal interactions · 2021Article
- Semaphorin 4D is a potential biomarker in pediatric leukemia and promotes leukemogenesis by activating PI3K/AKT and ERK signaling pathways.Oncology reports · 2021Article
- Interleukins as Mediators of the Tumor Cell-Bone Cell Crosstalk during the Initiation of Breast Cancer Bone Metastasis.International journal of molecular sciences · 2021Review
- Frequent Subgraph Mining of Functional Interaction Patterns Across Multiple Cancers.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2021Article
- The cancer cell secretome drives cooperative manipulation of the tumour microenvironment to accelerate tumourigenesis.Faculty reviews · 2021Review
- Circulating Tumor Cells Exhibit Metastatic Tropism and Reveal Brain Metastasis Drivers.Cancer discovery · 2020Article
- SEMA4D under the posttranscriptional regulation of HuR and miR-4319 boosts cancer progression in esophageal squamous cell carcinoma.Cancer biology & therapy · 2020Article
- Beyond Cell Motility: The Expanding Roles of Chemokines and Their Receptors in Malignancy.Frontiers in immunology · 2020Review
- What Is the Role of Interleukins in Breast Cancer Bone Metastases? A Systematic Review of Preclinical and Clinical Evidence.Cancers · 2019Review
- Plasma levels of Semaphorin 4D are decreased by adjuvant tamoxifen but not aromatase inhibitor therapy in breast cancer patients.Journal of bone oncology · 2019Article
- Semaphorin 4D promotes the proliferation and metastasis of bladder cancer by activating the PI3K/AKT pathway.Tumori · 2019Article
- Sema4D expression and secretion are increased by HIF-1α and inhibit osteogenesis in bone metastases of lung cancer.Clinical & experimental metastasis · 2019Article
- Adenosine AFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Bone density is controlled by interactions between osteoclasts, which resorb bone, and osteoblasts, which deposit it. The semaphorins and their receptors, the plexins, originally shown to function in the immune system and to provide chemotactic cues for axon guidance, are now known to play a role in this process as well. Emerging data have identified Semaphorin 4D (Sema4D) as a product of osteoclasts acting through its receptor Plexin-B1 on osteoblasts to inhibit their function, tipping the balance of bone homeostasis in favor of resorption. Breast cancers and other epithelial malignancies overexpress Sema4D, so we theorized that tumor cells could be exploiting this pathway to establish lytic skeletal metastases. Here, we use measurements of osteoblast and osteoclast differentiation and function in vitro and a mouse model of skeletal metastasis to demonstrate that both soluble Sema4D and protein produced by the breast cancer cell line MDA-MB-231 inhibits differentiation of MC3T3 cells, an osteoblast cell line, and their ability to form mineralized tissues, while Sema4D-mediated induction of IL-8 and LIX/CXCL5, the murine homologue of IL-8, increases osteoclast numbers and activity. We also observe a decrease in the number of bone metastases in mice injected with MDA-MB-231 cells when Sema4D is silenced by RNA interference. These results are significant because treatments directed at suppression of skeletal metastases in bone-homing malignancies usually work by arresting bone remodeling, potentially leading to skeletal fragility, a significant problem in patient management. Targeting Sema4D in these cancers would not affect bone remodeling and therefore could elicit an improved therapeutic result without the debilitating side effects.
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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.