Hirata Takeshi, Park Seung Chol, Muldong Michelle T, Wu Christina N, Yamaguchi Tomonori, Strasner Amy, Raheem Omer, Kumon Hiromi, Sah Robert L, Cacalano Nicholas A, Jamieson Catriona H M, Kane Christopher J, Masuda Koichi, Kulidjian Anna A, Jamieson Christina A M
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Urology, Wonkwang University School of Medicine and Hospital, Iksan, South Korea.
Asian J Urol. 2016 Oct;3(4):229-239. doi: 10.1016/j.ajur.2016.09.001. Epub 2016 Sep 12.
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 2 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 ( < 0.01) whereas BV ( < 0.05) and bone shaft diameter ( < 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.
骨转移发生在高达90%的晚期前列腺癌男性患者中，会导致骨折、剧痛和治疗抵抗。骨转移会引发一系列类型的骨病变，即使在个体前列腺癌患者中，这些病变对治疗的反应也可能不同。因此，骨的特殊环境使该疾病更加复杂且难以治愈。一种能够可重复诱导出反映患者所见复杂性的骨病变的模型，对于新型治疗方法的临床前测试将具有极高价值。对植入了PCSD1（一种来自前列腺癌骨转移手术标本的新的患者来源异种移植瘤）的小鼠股骨的微观结构变化进行了测定。
进行了定量微计算机断层扫描（显微CT）和组织学分析，以评估将PCSD1细胞或单独的培养基（对照）直接注射到2只雄性小鼠右股骨中的效果。
仅在注射了PCSD1细胞的小鼠股骨中形成了骨病变。股骨近端和远端的骨体积（BV）显著降低（<0.01），而沿股骨干的BV（<0.05）和骨干直径（<0.01）显著增加。
PCSD1细胞可重复诱导骨质流失，导致股骨末端出现溶骨性病变，相反，沿股骨干诱导异常骨形成，导致成骨性病变。因此，PCSD1细胞与不同骨区域特异性微环境的相互作用决定了骨病变的类型。我们的方法可用于确定不同骨区域是否支持更具治疗抵抗性的肿瘤生长，从而需要新型治疗方法。
