Heparanase inhibits osteoblastogenesis and shifts bone marrow progenitor cell fate in myeloma bone disease

Ruan, Jian; Trotter, Timothy N.; Li, Nan; Luo, Rong; Javed, Amjad; Sanderson, Ralph D.; Suva, Larry J.; Yang, Yang

doi:10.1016/j.bone.2013.07.024

Cited by 44 publications

(48 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8 Adipocytes and precursor cells secrete soluble molecules into the local microenvironment and bloodstream that serve to attract other cells, such as macrophages. 21 Therefore, we first determined whether preadipocytes and/or mature adipocyte-derived soluble molecules can directly attract MM cells.…”

Section: Adipocyte Lineage Cellederived Soluble Molecules Directly Atmentioning

confidence: 99%

“…8,11,31 We initially examined biopsy specimens from MM patients and weight-and age-matched healthy individuals to identify changes in adipocyte lineage cells. Interestingly, we found a significant increase in the number of preadipocytes, which express the preadipocyte marker Pref-1, in the BM of MM patients compared with healthy BM.…”

Section: Adipocytes Promote Myeloma Progressionmentioning

confidence: 99%

“…5,6 Numerous changes occur in the BM microenvironment as a response to MM cells, both at the primary tumor site and in distant sites. 7,8 The establishment of a premetastatic niche, in which distant sites become hospitable to cancer cells before metastasis occurs, is emerging as an important step in the progression of many cancers, including MM. 9 These alterations include enhanced angiogenesis, bone destruction, and modulation of immune cells, although the exact mechanisms driving these changes and the relative effect on MM pathogenesis remain unclear.…”

mentioning

confidence: 99%

“…11 However, we previously reported that MM cells not only inhibit osteoblastogenesis but also shift osteoblast progenitors toward adipogenesis. 8 Importantly, these changes also occur in distant bone sites before arrival of disseminating MM cells through soluble molecules secreted by MM cells. 8 Because both preadipocytes and mature, lipid-filled adipocytes are highly secretory, releasing a number of cytokines and hormones locally and systemically, we hypothesized that this increased adipogenesis in BM promotes MM progression and dissemination to new bone sites.…”

mentioning

confidence: 99%

“…8 Importantly, these changes also occur in distant bone sites before arrival of disseminating MM cells through soluble molecules secreted by MM cells. 8 Because both preadipocytes and mature, lipid-filled adipocytes are highly secretory, releasing a number of cytokines and hormones locally and systemically, we hypothesized that this increased adipogenesis in BM promotes MM progression and dissemination to new bone sites. 12 In the present study, we tested this hypothesis using in vivo and in vitro models and determined mechanisms of adipocyte action in MM.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Adipocyte-Lineage Cells Support Growth and Dissemination of Multiple Myeloma in Bone

Trotter

Gibson

Lama-Sherpa

et al. 2016

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Multiple myeloma (MM) cells reside in the bone marrow microenvironment and form complicated interactions with nonneoplastic, resident stromal cells. We previously found that aggressive MM cells shift osteoblast progenitors toward adipogenesis. In addition, adipocytes are among the most common cell types in the adult skeleton; both mature adipocytes and preadipocytes serve as endocrine cells that secrete a number of soluble molecules into the microenvironment. Therefore, we used a combination of in vivo and in vitro methods to test the hypothesis that an increase in adipocyte lineage cells feeds back to promote MM progression. The results of this study revealed that bone marrow from patients with MM indeed contains increased preadipocytes and significantly larger mature adipocytes than normal bone marrow. We also found that preadipocytes and mature adipocytes secrete many molecules important for supporting MM cells in the bone marrow and directly recruit MM cells through both monocyte chemotactic protein-1 and stromal cell-derived factor-1a. Co-culture experiments found that preadipocytes activate Wnt signaling and decrease cleaved caspase-3, whereas mature adipocytes activate ERK signaling in MM cells. Furthermore, mature adipocyte conditioned medium promotes MM growth, whereas co-culture with preadipocytes results in enhanced MM cell chemotaxis in vitro and increased tumor growth in bone in vivo. Combined, these data reveal the importance of preadipocytes and mature adipocytes on MM progression and represent a unique target in the bone marrow microenvironment. (Am J Pathol 2016, 186: 3054e3063; http://dx

show abstract

Section: Adipocyte Lineage Cellederived Soluble Molecules Directly Atmentioning

confidence: 99%

Section: Adipocytes Promote Myeloma Progressionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Adipocyte-Lineage Cells Support Growth and Dissemination of Multiple Myeloma in Bone

Trotter

Gibson

Lama-Sherpa

et al. 2016

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

show abstract

Epigenetic‐Based Mechanisms of Osteoblast Suppression in Multiple Myeloma Bone Disease

2019

View full text Add to dashboard Cite

Multiple myeloma (MM) bone disease is characterized by the development of osteolytic lesions, which cause severe complications affecting the morbidity, mortality, and treatment of myeloma patients. Myeloma tumors seeded within the bone microenvironment promote hyperactivation of osteoclasts and suppression of osteoblast differentiation. Because of this prolonged suppression of bone marrow stromal cells’ (BMSCs) differentiation into functioning osteoblasts, bone lesions in patients persist even in the absence of active disease. Current antiresorptive therapy provides insufficient bone anabolic effects to reliably repair MM lesions. It has become widely accepted that myeloma‐exposed BMSCs have an altered phenotype with pro‐inflammatory, immune‐modulatory, anti‐osteogenic, and pro‐adipogenic properties. In this review, we focus on the role of epigenetic‐based modalities in the establishment and maintenance of myeloma‐induced suppression of osteogenic commitment of BMSCs. We will focus on recent studies demonstrating the involvement of chromatin‐modifying enzymes in transcriptional repression of osteogenic genes in MM‐BMSCs. We will further address the epigenetic plasticity in the differentiation commitment of osteoprogenitor cells and assess the involvement of chromatin modifiers in MSC‐lineage switching from osteogenic to adipogenic in the context of the inflammatory myeloma microenvironment. Lastly, we will discuss the potential of employing small molecule epigenetic inhibitors currently used in the MM research as therapeutics and bone anabolic agents in the prevention or repair of osteolytic lesions in MM. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

show abstract

Involvement of Syndecan-1 and Heparanase in Cancer and Inflammation

Teixeira

Götte

2020

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

Heparanase inhibits osteoblastogenesis and shifts bone marrow progenitor cell fate in myeloma bone disease

Cited by 44 publications

References 36 publications

Adipocyte-Lineage Cells Support Growth and Dissemination of Multiple Myeloma in Bone

Adipocyte-Lineage Cells Support Growth and Dissemination of Multiple Myeloma in Bone

Epigenetic‐Based Mechanisms of Osteoblast Suppression in Multiple Myeloma Bone Disease

Involvement of Syndecan-1 and Heparanase in Cancer and Inflammation

Contact Info

Product

Resources

About