Specific bone region localization of osteolytic versus osteoblastic lesions in a patient-derived xenograft model of bone metastatic prostate cancer.
Specific bone region localization of osteolytic versus osteoblastic lesions in a patient-derived xenograft model of bone metastatic prostate cancer.
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DOI：
10.1016/j.ajur.2016.09.001
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发表时间：
2016-10
影响因子：
2.6
通讯作者：
Jamieson CAM
中科院分区：
文献类型：
--
作者：
Hirata T;Park SC;Muldong MT;Wu CN;Yamaguchi T;Strasner A;Raheem O;Kumon H;Sah RL;Cacalano NA;Jamieson CHM;Kane CJ;Masuda K;Kulidjian AA;Jamieson CAM
高达90%的晚期前列腺癌患者会发生骨转移，并会导致骨折、剧烈疼痛和治疗抵抗。骨转移导致一系列类型的骨损伤，即使在个别前列腺癌患者中，这些损伤对治疗的反应也可能不同。因此，骨骼的特殊环境使这种疾病变得更加复杂和不可治愈。一种可重复诱导骨损伤的模型，反映了患者体内的复杂性，对于新疗法的临床前测试将是无价的。对植入PCSD1的小鼠股骨的微结构变化进行了测定。PCSD1是一种来自外科前列腺癌骨转移标本的新的患者来源的异种移植。对RAG2、−/−γ、c、−/−雄性小鼠右侧股骨直接注射PCSD1细胞或单独注射培养液(对照组)的效果进行了定量显微CT和组织学分析。骨损伤只在注射PCSD1细胞的小鼠的股骨中形成。股骨近端和远端的骨体积(BV)显著减小(P<0.01)，而BV(P<0.05)和骨干径(P<0.01)沿股骨干显著增大。PCSD1细胞可重复地诱导骨丢失，导致股骨末端的溶骨性损害，相反，诱导异常的骨形成导致股骨骨干沿线的成骨损害。因此，PCSD1细胞与不同骨区域特定微环境的相互作用决定了骨损伤的类型。我们的方法可以用来确定不同的骨骼区域是否支持更多的耐药肿瘤生长，因此需要新的治疗方法。
Bone metastasis occurs in up to 90% of men with advanced prostate cancer and leads to fractures, severe pain and therapy-resistance. Bone metastases induce a spectrum of types of bone lesions which can respond differently to therapy even within individual prostate cancer patients. Thus, the special environment of the bone makes the disease more complicated and incurable. A model in which bone lesions are reproducibly induced that mirrors the complexity seen in patients would be invaluable for pre-clinical testing of novel treatments. The microstructural changes in the femurs of mice implanted with PCSD1, a new patient-derived xenograft from a surgical prostate cancer bone metastasis specimen, were determined. Quantitative micro-computed tomography (micro-CT) and histological analyses were performed to evaluate the effects of direct injection of PCSD1 cells or media alone (Control) into the right femurs of Rag2−/−γc−/− male mice. Bone lesions formed only in femurs of mice injected with PCSD1 cells. Bone volume (BV) was significantly decreased at the proximal and distal ends of the femurs (p < 0.01) whereas BV (p < 0.05) and bone shaft diameter (p < 0.01) were significantly increased along the femur shaft. PCSD1 cells reproducibly induced bone loss leading to osteolytic lesions at the ends of the femur, and, in contrast, induced aberrant bone formation leading to osteoblastic lesions along the femur shaft. Therefore, the interaction of PCSD1 cells with different bone region-specific microenvironments specified the type of bone lesion. Our approach can be used to determine if different bone regions support more therapy resistant tumor growth, thus, requiring novel treatments.