prikaz prve stranice dokumenta Melphalan modifies the bone microenvironment by enhancing osteoclast formation
  Download
PDF 10.05 MB
Scientific paper - Original scientific paper
Melphalan modifies the bone microenvironment by enhancing osteoclast formation
Oncotarget, 8 (2017), 40; 68047-6858. https://doi.org/10.18632/oncotarget.19152
Chai, Ryan C.; McDonald, Michelle M.; Terry, Rachael L.; Kovačić, Nataša; Down, Jenny M.; Pettitt, Jessica A.; Mohanty, Sindhu T.; Shah, Shruti; Haffari, Gholamreza; Xu, Jiake; Gillespie, Matthew T.; Rogers, Michael J.; Price, John T.; Croucher, Peter I.; Quinn, Julian M.W. More authors...

Cite this document

Chai, R. C., McDonald, M. M., Terry, R. L., Kovačić, N., Down, J. M., Pettitt, J. A. ... Quinn, J. M. (2017). Melphalan modifies the bone microenvironment by enhancing osteoclast formation. Oncotarget, 8. (40), 68047-6858. doi: 10.18632/oncotarget.19152

Chai, Ryan C., et al. "Melphalan modifies the bone microenvironment by enhancing osteoclast formation." Oncotarget, vol. 8, no. 40, 2017, pp. 68047-6858. https://doi.org/10.18632/oncotarget.19152

Chai, Ryan C., Michelle M. McDonald, Rachael L. Terry, Nataša Kovačić, Jenny M. Down, Jessica A. Pettitt, Sindhu T. Mohanty, et al. "Melphalan modifies the bone microenvironment by enhancing osteoclast formation." Oncotarget 8, no. 40 (2017): 68047-6858. https://doi.org/10.18632/oncotarget.19152

Chai, R. C., et al. (2017) 'Melphalan modifies the bone microenvironment by enhancing osteoclast formation', Oncotarget, 8(40), pp. 68047-6858. doi: 10.18632/oncotarget.19152

Chai RC, McDonald MM, Terry RL, Kovačić N, Down JM, Pettitt JA, and sur.. Melphalan modifies the bone microenvironment by enhancing osteoclast formation. Oncotarget [Internet]. 2017 July 10 [cited 2024 October 12];8(40):68047-6858. doi: 10.18632/oncotarget.19152

R. C. Chai, et al., "Melphalan modifies the bone microenvironment by enhancing osteoclast formation", Oncotarget, vol. 8, no. 40, pp. 68047-6858, July 2017. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:105:798910. [Accessed: 12 October 2024]

Please login to the repository to save this object to your list.
Metadata
Title (english)Melphalan modifies the bone microenvironment by enhancing osteoclast formation
AuthorRyan C. Chai
AuthorMichelle M. McDonald
AuthorRachael L. Terry
AuthorNataša Kovačić
AuthorJenny M. Down
AuthorJessica A. Pettitt
AuthorSindhu T. Mohanty
AuthorShruti Shah
AuthorGholamreza Haffari
AuthorJiake Xu
AuthorMatthew T. Gillespie
AuthorMichael J. Rogers
AuthorJohn T. Price
AuthorPeter I. Croucher
AuthorJulian M.W. Quinn
Author's institutionUniversity of Zagreb
School of Medicine
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Basic Medical Sciences
Abstract (english)
Melphalan is a cytotoxic chemotherapy used to treat patients with multiple myeloma (MM). Bone resorption by osteoclasts, by remodeling the bone surface, can reactivate dormant MM cells held in the endosteal niche to promote tumor development. Dormant MM cells can be reactivated after melphalan treatment; however, it is unclear whether melphalan treatment increases osteoclast formation to modify the endosteal niche. Melphalan treatment of mice for 14 days decreased bone volume and the endosteal bone surface, and this was associated with increases in osteoclast numbers. Bone marrow cells (BMC) from melphalan-treated mice formed more osteoclasts than BMCs from vehicle-treated mice, suggesting that osteoclast progenitors were increased. Melphalan also increased osteoclast formation in BMCs and RAW264.7 cells in vitro, which was prevented with the cell stress response (CSR) inhibitor KNK437. Melphalan also increased expression of the osteoclast regulator the microphthalmia-associated transcription factor (MITF), but not nuclear factor of activated T cells 1 (NFATc1). Melphalan increased expression of MITF-dependent cell fusion factors, dendritic cell-specific transmembrane protein (Dc-stamp) and osteoclast-stimulatory transmembrane protein (Oc-stamp) and increased cell fusion. Expression of osteoclast stimulator receptor activator of NFκB ligand (RANKL) was unaffected by melphalan treatment. These data suggest that melphalan stimulates osteoclast formation by increasing osteoclast progenitor recruitment and differentiation in a CSR-dependent manner. Melphalan-induced osteoclast formation is associated with bone loss and reduced endosteal bone surface. As well as affecting bone structure this may contribute to dormant tumor cell activation, which has implications for how melphalan is used to treat patients with MM.
Languageenglish
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review
Publication versionPublished version
Journal titleOncotarget
Numberingvol. 8, no. 40, pp. 68047-6858
p-ISSN1949-2553
DOIhttps://doi.org/10.18632/oncotarget.19152
URN:NBNurn:nbn:hr:105:798910
Publication2017-07-10
Document URLhttps://doi.org/10.18632/oncotarget.19152
Type of resourceText
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2024-03-28 09:15:42