ArticleHaematologica2010
Hypoxia-inducible factor-2 is a novel regulator of aberrant CXCL12 expression in multiple myeloma plasma cells.
Article in Haematologica, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 94 citations in OpenAlex.
- The role of antioxidants in multiple myeloma: diagnostic, prognostic, and therapeutic applications: a narrative review.Therapeutic advances in hematology · 2026Review
- mTOR activity and metabolic reprogramming of CD8+ T cells is impaired under hypoxia and within the multiple myeloma bone marrow.Blood advances · 2025Article
- Targeting the CXCR4/CXCL12 Axis to Overcome Drug Resistance in Triple-Negative Breast Cancer.Cells · 2025Review
- The implication of serum HLA-G in angiogenesis of multiple myeloma.Molecular medicine (Cambridge, Mass.) · 2024Article
- Solitary hyoid plasmacytoma with unicentric Castleman disease: A case report and review of literature.World journal of clinical cases · 2022Article
- Targeting hypoxia in solid and haematological malignancies.Journal of experimental & clinical cancer research : CR · 2022Review
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- Review
- Article
- The Role of Marrow Microenvironment in the Growth and Development of Malignant Plasma Cells in Multiple Myeloma.International journal of molecular sciences · 2021Review
- CXCL12 enhances pregnancy outcome via improvement of endometrial receptivity in mice.Scientific reports · 2021Article
- Review
- The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors-A Review of Literature.International journal of molecular sciences · 2021Review
- Tumour Dissemination in Multiple Myeloma Disease Progression and Relapse: A Potential Therapeutic Target in High-Risk Myeloma.Cancers · 2020Review
- The role of hypoxia-inducible factors in neovascular age-related macular degeneration: a gene therapy perspective.Cellular and molecular life sciences : CMLS · 2020Review
- Primary prostate cancer educates bone stroma through exosomal pyruvate kinase M2 to promote bone metastasis.The Journal of experimental medicine · 2019Article
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- Hypoxia as a barrier to immunotherapy in pancreatic adenocarcinoma.Clinical and translational medicine · 2019Review
- Molecular Players in Hematologic Tumor Cell Trafficking.Frontiers in immunology · 2019Review
- Therapeutic Targeting of Vascular Remodeling and Right Heart Failure in Pulmonary Arterial Hypertension with a HIF-2α Inhibitor.American journal of respiratory and critical care medicine · 2018Article
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Authors and funding
9 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMultiple myeloma is an incurable malignancy of bone marrow plasma cells. Progression of multiple myeloma is accompanied by an increase in bone marrow angiogenesis. Studies from our laboratory suggest a role for the CXCL12 chemokine in this process, with circulating levels of CXCL12 correlating with bone marrow angiogenesis in patients with multiple myeloma. While the mechanisms responsible for aberrant plasma cell expression of CXCL12 remain to be determined, studies in other systems suggest a role for hypoxia and hypoxia-inducible transcription factors. DESIGN AND
methodsThe expression of hypoxia-inducible factor protein was examined in patients' bone marrow biopsy specimens using immunohistochemistry. The hypoxic regulation of CXCL12 was examined in multiple myeloma plasma cell lines using polymerase chain reaction and western blotting. The role of hypoxia-inducible factors-1 and -2 in the regulation of CXCL12 expression was examined using over-expression and short hairpin RNA knockdown constructs, electrophoretic mobility shift assays and chromatin immunoprecipitation. The contribution of CXCL12 to hypoxia-induced angiogenesis was examined in vivo using a subcutaneous murine model of neovascularization.
resultsStrong hypoxia-inducible factor-2 protein expression was detected in CD138(+) multiple myeloma plasma cells in patients' biopsy specimens. Prolonged exposure to hypoxia strongly up-regulated CXCL12 expression in multiple myeloma plasma cells and hypoxia-inducible factor-2 was found to play a key role in this response. Promoter analyses revealed increased hypoxia-inducible factor-2 binding to the CXCL12 promoter under hypoxic conditions. Over-expression of hypoxia-inducible factor in multiple myeloma plasma cells strongly induced in vivo angiogenesis, and administration of a CXCL12 antagonist decreased hypoxia-inducible factor-induced angiogenesis.
conclusionsHypoxia-inducible factor-2 is a newly identified regulator of CXCL12 expression in multiple myeloma plasma cells and a major contributor to multiple myeloma plasma cell-induced angiogenesis. Targeting the hypoxic niche, and more specifically hypoxia-inducible factor-2, may represent a viable strategy to inhibit angiogenesis in multiple myeloma and progression of this disease.
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