ArticleCancer research2016
Galectin-3 Cleavage Alters Bone Remodeling: Different Outcomes in Breast and Prostate Cancer Skeletal Metastasis.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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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
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Survival and functional outcomes following surgical repair of pathological fractures in dogs: A meta-analysis.Open veterinary journal · 2025Pooled it
- Modified Citrus Pectin Treatment in Non-Metastatic Biochemically Relapsed Prostate Cancer: Results of a Prospective Phase II Study.Nutrients · 2021Trial
- The influence of PSA autoantibodies in prostate cancer patients: a prospective clinical study-II.Oncotarget · 2017Trial
- The glycobiology of prostate cancer: an update.Oncogene · 2026Review
- Article
- Prostate Cancer Biomarkers with a Focus on Galectin-3: Emerging Clinical and Therapeutic Implications.Current oncology (Toronto, Ont.) · 2026Review
- Galectin-3-integrin α5β1 phase separation disrupted by advanced glycation end-products impairs diabetic wound healing in rodents.Nature communications · 2025Article
- Inflammaging-Driven Osteoporosis: Is a Galectin-Targeted Approach Needed?International journal of molecular sciences · 2025Review
- Revisiting Multi-Omics Data to Unravel Galectins as Prognostic Factors in Head and Neck Squamous Cell Carcinoma.Biomedicines · 2024Article
- Multiple influence of immune cells in the bone metastatic cancer microenvironment on tumors.Frontiers in immunology · 2024Review
- Glycobiology in osteoclast differentiation and function.Bone research · 2023Review
- Prostate cancer bone metastases biology and clinical management (Review).Oncology letters · 2023Review
- Targeting galectin-driven regulatory circuits in cancer and fibrosis.Nature reviews. Drug discovery · 2023Review
- Galectin-3 in prostate cancer and heart diseases: a biomarker for these two frightening pathologies?Molecular biology reports · 2023Review
- Galectins as pivotal components in oncogenesis and immune exclusion in human malignancies.Frontiers in immunology · 2023Review
- Galectin-1 and Galectin-3 in B-Cell Precursor Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2022Article
- NKX2-8/PTHrP Axis-Mediated Osteoclastogenesis and Bone Metastasis in Breast Cancer.Frontiers in oncology · 2022Article
- Galectin-3 Contributes to the Inhibitory Effect of lα,25-(OH)International journal of molecular sciences · 2021Article
- Overcoming Microenvironment-Mediated Chemoprotection through Stromal Galectin-3 Inhibition in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2021Article
- The Role of Galectin-3 in 1α,25(OH)Veterinary sciences · 2021Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Management of bone metastasis remains clinically challenging and requires the identification of new molecular target(s) that can be therapeutically exploited to improve patient outcome. Galectin-3 (Gal-3) has been implicated as a secreted factor that alters the bone microenvironment. Proteolytic cleavage of Gal-3 may also contribute to malignant cellular behaviors, but has not been addressed in cancer metastasis. Here, we report that Gal-3 modulates the osteolytic bone tumor microenvironment in the presence of RANKL. Gal-3 was localized on the osteoclast cell surface, and its suppression by RNAi or a specific antagonist markedly inhibited osteoclast differentiation markers, including tartrate-resistant acid phosphatase, and reduced the number of mature osteoclasts. Structurally, the 158-175 amino acid sequence in the carbohydrate recognition domain (CRD) of Gal-3 was responsible for augmented osteoclastogenesis. During osteoclast maturation, Gal-3 interacted and colocalized with myosin-2A along the surface of cell-cell fusion. Pathologically, bone metastatic cancers expressed and released an intact form of Gal-3, mainly detected in breast cancer bone metastases, as well as a cleaved form, more abundant in prostate cancer bone metastases. Secreted intact Gal-3 interacted with myosin-2A, leading to osteoclastogenesis, whereas a shift to cleaved Gal-3 attenuated the enhancement in osteoclast differentiation. Thus, our studies demonstrate that Gal-3 shapes the bone tumor microenvironment through distinct roles contingent on its cleavage status, and highlight Gal-3 targeting through the CRD as a potential therapeutic strategy for mitigating osteolytic bone remodeling in the metastatic niche.
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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.