Anti-α4 integrin antibody suppresses the development of multiple myeloma and associated osteoclastic osteolysis

Mori, Yoshihito; Shimizu, Nobuaki; Dallas, Mark; Niewolna, Maria; Story, Beryl; Williams, Paul J.; Mundy, Gregory R.; Yoneda, Toshiyuki

doi:10.1182/blood-2004-01-0236

Cited by 163 publications

(106 citation statements)

References 28 publications

(23 reference statements)

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“…Interactions between alpha4-beta1 integrin and vascular cell adhesion molecule 1 (VCAM-1) have been demonstrated to increase the production of osteoclast stimulating activity, which could not be attributed to IL-6, TNF or PTHrP (46). Furthermore, inhibition of this activity, using a monoclonal antibody to alpha4 integrin was found to inhibit the development of multiple myeloma and the associated osteolysis in the 5TGM1 murine model of myeloma (47). Interactions between bone marrow stromal cells and myeloma cells have also been demonstrated to increase the expression of RANKL by the bone marrow stromal cells, with data supporting a role for the VCAM-1-α4b1 interaction (48).…”

Section: Cell-cell Interactionsmentioning

confidence: 99%

The pathogenesis of the bone disease of multiple myeloma

Edwards

Zhuang

Mundy

2008

Bone

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Multiple myeloma is a fatal hematologic malignancy associated with clonal expansion of malignant plasma cells within the bone marrow and the development of a destructive osteolytic bone disease. The principal cellular mechanisms involved in the development of myeloma bone disease are an increase in osteoclastic bone resorption, and a reduction in bone formation. Myeloma cells are found in close association with sites of active bone resorption, and the interactions between myeloma cells, and other cells within the specialized bone marrow microenvironment are essential, both for tumor growth and the development of myeloma bone disease. This review discusses the many different factors which have been implicated in myeloma bone disease, including the evidence for their role in myeloma and subsequent therapeutic implications.

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Section: Cell-cell Interactionsmentioning

confidence: 99%

The pathogenesis of the bone disease of multiple myeloma

Edwards

Zhuang

Mundy

2008

Bone

Self Cite

150

120

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“…Several laboratories have reported that myeloma cells produce low levels of RANKL; however, it is unclear if these levels are sufficient to support osteoclast formation. 35 -38 Myeloma cells do induce production of high levels of RANKL by marrow stromal cells through adhesive interactions between 4 1 integrin on myeloma cells and vascular cell adhesion molecule-1 (VCAM-1) on marrow stromal cells, 39 as well as by soluble factors produced by myeloma cells, such as TNF- 28,40 and Dickkopf1 (DKK1). 41 Further enhancing the effects of increased RANKL in myeloma is the decreased production of OPG by marrow stromal cells via inhibition of osteoblast differentiation, decreased transcription of OPG and degradation of OPG by myeloma cell endocytosis of the OPG bound to CD138 (syndecan-1).…”

Section: Factors Driving Osteoclast Formation and Activity In Mmbdmentioning

confidence: 99%

Mechanisms of multiple myeloma bone disease

Galson¹,

Silbermann²,

Roodman³

2012

BoneKEy Reports

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Multiple myeloma is the second most common hematological malignancy and the most frequent cancer to involve the skeleton. Multiple myeloma bone disease (MMBD) is characterized by abnormal bone remodeling with dysfunction of both bone resorption and bone formation, and thus can be used as a paradigm for other inflammatory bone diseases, and the regulation of osteoclasts and osteoblasts in malignancy. Studies of MMBD have identified novel regulators that increase osteoclastogenesis and osteoclast function, repress osteoblast differentiation, increase angiogenesis, or permanently alter stromal cells. This review will discuss the current understanding of mechanisms of osteoclast and osteoblast regulation in MMBD, and therapeutic approaches currently in use and under development that target mediators of bone destruction and blockade of bone formation for myeloma patients, including new anabolic therapies.

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“…The spleen is a hematopoietic organ in mice and myeloma cells have been show to localize in both spleen and bone marrow in mouse models. 85 In two out of three treated mice, we were able to recover VSV-GFP from spleen tissue (data not shown). As expected, VSV was not recovered from the control group animals (data not shown).…”

Section: In Vivo Trafficking and Antitumor Activity Of Vsv-infected 5mentioning

confidence: 91%