ArticleCancer research2010
Heparanase enhances local and systemic osteolysis in multiple myeloma by upregulating the expression and secretion of RANKL.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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
42 citing papers in PubMed, 65 citations in OpenAlex.
- Glycobiology in osteoclast differentiation and function.Bone research · 2023Review
- Heparanase-A single protein with multiple enzymatic and nonenzymatic functions.Proteoglycan research · 2023Review
- Effect of HPSE and HPSE2 SNPs on the Risk of Developing Primary Paraskeletal Multiple Myeloma.Cells · 2023Article
- Review
- Heparanase-enhanced Shedding of Syndecan-1 and Its Role in Driving Disease Pathogenesis and Progression.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
- Significance of host heparanase in promoting tumor growth and metastasis.Matrix biology : journal of the International Society for Matrix Biology · 2020Article
- Nuclear Heparanase Regulates Chromatin Remodeling, Gene Expression and PTEN Tumor Suppressor Function.Cells · 2020Article
- Heparanase promotes myeloma stemness and in vivo tumorigenesis.Matrix biology : journal of the International Society for Matrix Biology · 2020Article
- Topical application of Heparanase-1 facilitates bone remodeling during the healing of bone defects in a mouse model.Journal of the Chinese Medical Association : JCMA · 2020Article
- Runx2 Deficiency in Osteoblasts Promotes Myeloma Progression by Altering the Bone Microenvironment at New Bone Sites.Cancer research · 2020Article
- Heparanase: A Dynamic Promoter of Myeloma Progression.Advances in experimental medicine and biology · 2020Review
- Extracellular Vesicles Enhance Multiple Myeloma Metastatic Dissemination.International journal of molecular sciences · 2019Review
- Surgical thyroparathyroidectomy prevents progression of 5TGM1 murine multiple myelomaJournal of bone oncology · 2018Review
- Chemotherapy induces secretion of exosomes loaded with heparanase that degrades extracellular matrix and impacts tumor and host cell behavior.Matrix biology : journal of the International Society for Matrix Biology · 2018Article
- Mesenchymal stem cells expressing osteoprotegerin variants inhibit osteolysis in a murine model of multiple myeloma.Blood advances · 2017Article
- Heparanase Upregulation Contributes to Porcine Reproductive and Respiratory Syndrome Virus Release.Journal of virology · 2017Article
- NEK2 induces osteoclast differentiation and bone destruction via heparanase in multiple myeloma.Leukemia · 2017Article
- Heparanase overexpression down-regulates syndecan-1 expression in a gallbladder carcinoma cell line.The Journal of international medical research · 2017Article
- The Heparanase Inhibitor PG545 Attenuates Colon Cancer Initiation and Growth, Associating with Increased p21 Expression.Neoplasia (New York, N.Y.) · 2017Article
- Heparanase regulation of cancer, autophagy and inflammation: new mechanisms and targets for therapy.The FEBS journal · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Excessive bone destruction is a major cause of morbidity in myeloma patients. However, the biological mechanisms involved in the pathogenesis of myeloma-induced bone disease are not fully understood. Heparanase, an enzyme that cleaves the heparan sulfate chains of proteoglycans, is upregulated in a variety of human tumors, including multiple myeloma. We previously showed that heparanase promotes robust myeloma tumor growth and supports spontaneous metastasis of tumor cells to bone. In the present study, we show, for the first time, that the expression of heparanase by myeloma tumor cells remarkably enhances bone destruction locally within the tumor microenvironment. In addition, enhanced heparanase expression in the primary tumor also stimulated systemic osteoclastogenesis and osteolysis, thus mimicking the systemic osteoporosis often seen in myeloma patients. These effects occur, at least in part, as the result of a significant elevation in the expression and secretion of receptor activator of NF-κB ligand (RANKL) by heparanase-expressing myeloma cells. Moreover, analysis of bone marrow biopsies from myeloma patients reveals a positive correlation between the level of expression of heparanase and RANKL. Together, these discoveries reveal a novel and key role for heparanase in promoting tumor osteolysis and show that RANKL is central to the mechanism of heparanase-mediated osteolysis in myeloma.
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.