Prostate cancer metastases alter bone mineral and matrix composition independent of effects on bone architecture in mice--a quantitative study using microCT and Raman spectroscopy.
Prostate cancer metastases alter bone mineral and matrix composition independent of effects on bone architecture in mice--a quantitative study using microCT and Raman spectroscopy.
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DOI：
10.1016/j.bone.2013.07.006
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发表时间：
2013-10
期刊：
影响因子：
4.1
通讯作者：
Mahadevan-Jansen, Anita
中科院分区：
文献类型：
--
作者：
Bi, Xiaohong;Sterling, Julie A.;Merkel, Alyssa R.;Perrien, Daniel S.;Nyman, Jeffry S.;Mahadevan-Jansen, Anita
关键词：
前列腺癌是最常见的原发性肿瘤，也是美国男性癌症相关死亡的第二大原因。前列腺癌骨转移的特征在于异常的骨重建过程，并导致各种骨骼疾病。预防骨骼并发症是前列腺癌治疗的关键因素。本研究使用拉曼光谱和显微计算机断层扫描（microCT）研究了前列腺癌诱导的前列腺癌小鼠模型转移骨的分子组成和形态结构的改变。将LNCaP C4-2B前列腺癌细胞注射到5周龄雄性SCID小鼠的右胫骨中。在肿瘤接种后8周处死时，10个荷瘤小鼠中有2个在X线照片中仅显示成骨细胞病变，4个仅显示溶骨性病变，4个混合有成骨细胞和溶骨性病变。与对侧对照组相比，完整的荷瘤胫骨皮质中的碳酸盐替代显著增加，而胶原矿化水平、矿物结晶度和碳酸盐：基质比显著降低。MicroCT分析显示，溶骨性病变的胫骨骨体积/总体积、骨小梁数量和骨小梁厚度显著减少，骨表面/体积比显著增加，表明骨重建和骨丢失活跃。骨组成特性的变化与X线片的病变面积或microCT的骨结构变化无关。这项研究表明，LNCaP C4-2B前列腺癌转移改变骨组织组成的结构变化无关，改变骨质量可能是这些患者骨折风险的重要因素。拉曼光谱为研究肿瘤与骨微环境的相互作用提供了新的途径。
Prostate cancer is the most common primary tumor and the second leading cause of cancer-related deaths in men in the United States. Prostate cancer bone metastases are characterized by abnormal bone remodeling processes and result in a variety of skeletal morbidities. Prevention of skeletal complications is a crucial element in prostate cancer management. This study investigated prostate cancer-induced alterations in the molecular composition and morphological structure of metastasis-bearing bones in a mouse model of prostate cancer using Raman spectroscopy and micro-computed tomography (microCT). LNCaP C4-2B prostate cancer cells were injected into the right tibiae of 5-week old male SCID mice. Upon sacrifice at 8 weeks post tumor inoculation, two out of the ten tumor-bearing tibiae showed only osteoblastic lesions in the radiographs, 4 osteolytic lesions only and 4 mixed with osteoblastic and osteolytic lesions.. Carbonate substitution was significantly increased while there was a marked reduction in the level of collagen mineralization, mineral crystallinity, and carbonate:matrix ratio in the cortex of the intact tumor-bearing tibiae compared to contralateral controls. MicroCT analysis revealed a significant reduction in bone volume/total volume, trabecular number and trabecular thickness, as well as significant increase in bone surface/volume ratio in tibiae with osteolytic lesions, suggesting active bone remodeling and bone loss. None of the changes in bone compositional properties were correlated with lesion area from radiographs or the changes in bone architecture from microCT. This study indicates that LNCaP C4-2B prostate cancer metastases alter bone tissue composition independent of changes in architecture, and altered bone quality may be an important contributor to fracture risk in these patients. Raman spectroscopy may provide a new avenue of investigation into interactions between tumor and bone microenvironment.
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影响因子：
2.4
作者：
Bi, Xiaohong;Patil, Chetan A.;Nyman, Jeffry S.
通讯作者：
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影响因子：
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