Characterization of a new renal cell carcinoma bone metastasis mouse model
Characterization of a new renal cell carcinoma bone metastasis mouse model
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DOI：
10.1007/s10585-010-9329-9
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发表时间：
2010-05-01
影响因子：
4
通讯作者：
Kakonen, Sanna-Maria
中科院分区：
文献类型：
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作者：
Strube, Anne;Stepina, Elizaveta;Kakonen, Sanna-Maria
由肾细胞癌（RCC）引起的转移性骨病频繁发生，并且变得越来越普遍，这可能是因为患有播散性癌症的患者的生存时间不断增加。肾细胞癌骨转移患者会遭受剧烈疼痛、神经压迫综合征和病理性骨折。关于肾细胞癌骨骼转移的机制知之甚少。因此，为了更好地了解肾细胞癌（RCC）骨转移的分子机制，开发新的动物模型至关重要。我们通过将人786-O/荧光素酶细胞接种到无胸腺裸鼠的左心室中，建立了一种新的肾细胞癌骨转移动物模型。通过放射线照相和显微 CT 扫描监测，动物出现了严重的溶骨性骨破坏，平均终点为 62 +/- A 8 天。观察到的广泛骨质破坏与临床情况相当，主要发生在后肢、前肢和脊柱。肿瘤主要位于骨内并导致皮质骨破坏。 BLI 或组织形态计量学未检测到软组织转移。为了增加 786-O 细胞系的骨转移潜力，进行了体内选择，产生了导致溶骨性病变的亚群，平均终点为 47 +/- A 3 天。与亲代细胞系相比，选定的亚系在体外分泌更多的促血管生成因子 VEGF 和 bFGF，表明这些肿瘤是高度血管化的。该模型提供了临床情况的可靠再现，因此适合设计和评估更有效的肾细胞癌骨转移治疗方法。
Metastatic bone disease caused by renal cell carcinoma (RCC) occurs frequently and becomes more and more prevalent presumably because survival times among patients with disseminated cancers are increasing. Patients with bone metastases from renal cell carcinoma suffer from severe pain, nerve compression syndromes and pathologic fractures. Very little is known about the mechanisms of skeletal metastases of RCC. Thus, to better understand the molecular mechanism of renal cell cancer (RCC) bone metastasis, it is crucial to develop new animal models. We have established a new animal model of RCC metastasis to bone by inoculation of human 786-O/luciferase cells into the left cardiac ventricle of athymic nude mice. The animals developed aggressive osteolytic bone destruction as monitored by radiography and micro-CT-scans with the mean endpoint at 62 +/- A 8 days. The extensive bone destruction observed was comparable to the clinical setting and mainly occurred in hind limbs, forelimbs and the spine. The tumors were primarily located within the bone and resulted in destruction of cortical bone. No soft tissue metastases were detected by BLI or histomorphometry. To increase the bone-metastatic potential of the 786-O cell line, an in vivo selection was done yielding a subpopulation causing osteolytic lesions with the mean endpoint of 47 +/- A 3 days. The selected subline secreted more proangiogenic factors VEGF and bFGF in vitro compared to the parental cell line suggesting that these tumors are highly vascular. This model provides a reliable reproduction of the clinical situation and therefore, is suitable for designing and evaluating more effective treatments for RCC bone metastasis.