Increased bone remodeling due to ovariectomy dramatically increases tumoral growth in the 5T2 multiple myeloma mouse model
Increased bone remodeling due to ovariectomy dramatically increases tumoral growth in the 5T2 multiple myeloma mouse model
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DOI：
10.1016/s8756-3282(03)00196-0
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发表时间：
2003-09-01
期刊：
影响因子：
4.1
通讯作者：
Chappard, D
中科院分区：
文献类型：
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作者：
Libouban, H;Moreau, MF;Chappard, D
骨破坏是多发性骨髓瘤（MM）的主要临床后果。众所周知，骨髓瘤细胞与骨细胞之间存在“恶性循环”，浆细胞刺激骨细胞，骨细胞刺激肿瘤生长。我们假设卵巢切除术（OVX）诱导的加速骨重塑可以为骨髓瘤细胞生长提供更肥沃的环境。对C57BL/KaLwRij小鼠进行卵巢切除术导致小梁骨体积减少，破骨细胞数量增加。为了验证我们的假设，我们在注射5T2MM骨髓瘤细胞前一周切除了C57BL/KaLwRij小鼠的卵巢。以非ovx 5T2MM组为对照。卵巢切除术增加了肿瘤的生长，并诱发了早期溶骨病变的发展。OVX 5T2MM小鼠在10周时被安乐死，而非OVX 5T2MM小鼠在16周时被安乐死，因为OVX动物的疾病发展加速。用帕米膦酸钠治疗OVX 5T2MM小鼠可减少骨溶解，但对肿瘤的时间发展影响不大。这个联合模型（卵巢切除+ 5T2MM）证实了骨髓瘤细胞和骨髓瘤细胞的相互依赖性，并可以解释人类中惰性MM突然变为侵袭性MM的原因。(C) 2003 Elsevier Inc.版权所有。
Bone destruction is the main clinical consequence of multiple myeloma (MM). It is known that a "vicious circle" exists between bone and myeloma cells with plasma cells stimulating bone cells, which in return stimulate the neoplastic growth. We hypothesized that an accelerated bone remodeling induced by ovariectomy (OVX) could provide a more fertile environment for the myeloma cell growth. Ovariectomy performed on C57BL/KaLwRij mice resulted in reduced trabecular bone volume and increased osteoclast number. To test our hypothesis, we ovariectomzed C57BL/KaLwRij mice one week before injection of 5T2MM myeloma cells. A non-OVX 5T2MM group was used as control. Ovariectomy increased the tumor growth and induced an earlier development of osteolytic lesions. OVX 5T2MM mice were euthanazied at 10 weeks, instead of 16 weeks, for the non-OVX 5T2MM, mice because of the accelerated development of disease in OVX animals. Treatment of OVX 5T2MM mice with pamidronate reduced osteolysis but had little effect on the time development of the tumor. This combined model (ovariectomy + 5T2MM) confirmed the interdependence of bone and myeloma cells and could explain the some sudden burden of indolent MM into aggressive MM in humans. (C) 2003 Elsevier Inc. All rights reserved.