Melphalan modifies the bone microenvironment by enhancing osteoclast formation.

Melphalan modifies the bone microenvironment by enhancing osteoclast formation.
Oncotarget. 2017 Jul 10;:
Authors: Chai RC, McDonald MM, Terry RL, Kovačić N, Down JM, Pettitt JA, Mohanty ST, Shah S, Haffari G, Xu J, Gillespie MT, Rogers MJ, Price JT, Croucher PI, Quinn JMW
Abstract
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 ...

Source: Oncotarget - July 31, 2017 Category: Cancer & Oncology Tags: Oncotarget Source Type: research