Mesenchymal stem cells expressing osteoprotegerin variants inhibit osteolysis in a murine model of multiple myeloma

Higgs, Jerome T.; Lee, Joo Hyoung; Wang, Hong; Ramani, Vishnu C.; Chanda, Diptiman; Hardy, Cherlene Y.; Sanderson, Ralph D.; Ponnazhagan, Selvarangan

doi:10.1182/bloodadvances.2017007310

Cited by 9 publications

(3 citation statements)

References 57 publications

(67 reference statements)

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“…In addition to binding to RANKL to inhibit bone resorption, OPG also combines with TRAIL to exert an anti-apoptotic effect, thus limiting the clinical applications of OPG in cancer patients. Special genetically engineered MSCs overexpressing OPG that selectively bind to RANKL, but not to TRAIL were designed by Qiang et al As expected, the osteoclast activity induced by tumor cells expressing mutant OPG was significantly suppressed, suggesting the potential therapeutic value of this technology [ 89 ]. This provided clues for us to develop OPG-related therapeutics with fewer side effects and greater efficacy.…”

Section: Molecular Structure and Expression Of Opgmentioning

confidence: 99%

The roles of osteoprotegerin in cancer, far beyond a bone player

et al. 2022

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Osteoprotegerin (OPG), also known as tumor necrosis factor receptor superfamily member 11B (TNFRSF11B), is a member of the tumor necrosis factor (TNF) receptor superfamily. Characterized by its ability to bind to receptor activator of nuclear factor kappa B ligand (RANKL), OPG is critically involved in bone remodeling. Emerging evidence implies that OPG is far beyond a bone-specific modulator, and is involved in multiple physiological and pathological processes, such as immunoregulation, vascular function, and fibrosis. Notably, numerous preclinical and clinical studies have been conducted to assess the participation of OPG in tumorigenesis and cancer development. Mechanistic studies have demonstrated that OPG is involved in multiple hallmarks of cancer, including tumor survival, epithelial to mesenchymal transition (EMT), neo-angiogenesis, invasion, and metastasis. In this review, we systematically summarize the basis and advances of OPG from its molecular structure to translational applications. In addition to its role in bone homeostasis, the physiological and pathological impacts of OPG on human health and its function in cancer progression are reviewed, providing a comprehensive understanding of OPG. We aim to draw more attention to OPG in the field of cancer, and to propose it as a promising diagnostic or prognostic biomarker as well as potential therapeutic target for cancer.

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Section: Molecular Structure and Expression Of Opgmentioning

confidence: 99%

The roles of osteoprotegerin in cancer, far beyond a bone player

et al. 2022

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“…This interaction also accounts for bone destruction, a hallmark of late-stage myeloma that significantly deteriorates the quality of life of MM patients [ 19 ] . Indeed, the development of osteolytic lesions, present in more than 80% of myeloma patients [ 20 ] , is one of the most devastating consequences of advanced MM, caused by an imbalance between bone formation and resorption, partly due to a significant reduction in circulating osteoprotegerin [ 21 ] .…”

Section: Introductionmentioning

confidence: 99%

MYC inhibitors in multiple myeloma

Martínez-Martín¹,

Soucek²

2021

CDR

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“…The most widely used models rely on in vivo propagation of human myeloma cells in immunodeficient hosts (human-in-mouse xenografting) (12)(13)(14) or myeloma-like plasma cells from C57BL/6 (B6) (15) or BALB/c (C) mice (16) in genetically compatible (syngeneic) immunocompetent hosts (mouse-in-mouse autografting). Both strategies have made and continue to make important contributions to myeloma research (17,18), but are hampered by the reality that in vivo transfer of malignant cells (tumor transplantation) is not suitable for studying tumor development (oncogenesis). In other words, xeno-and autografting of neoplastic plasma cells bypasses the natural course of human myelomagenesis that begins with monoclonal gammopathy of undetermined significance (MGUS) (19), progresses to smoldering myeloma (SMM) (20), and eventually transitions to frank neoplasia (NDMM).…”

Section: Introductionmentioning

confidence: 99%

Laboratory Mice – A Driving Force in Immunopathology and Immunotherapy Studies of Human Multiple Myeloma

et al. 2021

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Mouse models of human cancer provide an important research tool for elucidating the natural history of neoplastic growth and developing new treatment and prevention approaches. This is particularly true for multiple myeloma (MM), a common and largely incurable neoplasm of post-germinal center, immunoglobulin-producing B lymphocytes, called plasma cells, that reside in the hematopoietic bone marrow (BM) and cause osteolytic lesions and kidney failure among other forms of end-organ damage. The most widely used mouse models used to aid drug and immunotherapy development rely on in vivo propagation of human myeloma cells in immunodeficient hosts (xenografting) or myeloma-like mouse plasma cells in immunocompetent hosts (autografting). Both strategies have made and continue to make valuable contributions to preclinical myeloma, including immune research, yet are ill-suited for studies on tumor development (oncogenesis). Genetically engineered mouse models (GEMMs), such as the widely known Vκ*MYC, may overcome this shortcoming because plasma cell tumors (PCTs) develop de novo (spontaneously) in a highly predictable fashion and accurately recapitulate many hallmarks of human myeloma. Moreover, PCTs arise in an intact organism able to mount a complete innate and adaptive immune response and tumor development reproduces the natural course of human myelomagenesis, beginning with monoclonal gammopathy of undetermined significance (MGUS), progressing to smoldering myeloma (SMM), and eventually transitioning to frank neoplasia. Here we review the utility of transplantation-based and transgenic mouse models of human MM for research on immunopathology and -therapy of plasma cell malignancies, discuss strengths and weaknesses of different experimental approaches, and outline opportunities for closing knowledge gaps, improving the outcome of patients with myeloma, and working towards a cure.

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Mesenchymal stem cells expressing osteoprotegerin variants inhibit osteolysis in a murine model of multiple myeloma

Abstract: Key Points• The study developed a mouse model of bone disseminated myeloma disease as in humans.• The study established therapeutic potential of OPG variants to revert myeloma bone damage in vivo.

Cited by 9 publications

References 57 publications

The roles of osteoprotegerin in cancer, far beyond a bone player

The roles of osteoprotegerin in cancer, far beyond a bone player

MYC inhibitors in multiple myeloma

Laboratory Mice – A Driving Force in Immunopathology and Immunotherapy Studies of Human Multiple Myeloma

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