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骨转移的大鼠模型

Rat models of bone metastases.

作者信息

Blouin Stéphane, Baslé Michel Félix, Chappard Daniel

机构信息

Faculté de Médecine, INSERM, EMI 0335-LHEA, 49045 ANGERS Cedex, France.

出版信息

Clin Exp Metastasis. 2005;22(8):605-14. doi: 10.1007/s10585-006-9002-5. Epub 2006 May 3.

Abstract

Bone metastases occur frequently in patients with advanced breast or prostate cancer. Bone metastases can be predominantly osteolytic, osteoblastic or mixed. Studies with animal models allow advances in understanding the molecular basis for bone metastases and provide new targets for therapy. Several animal models have been developed in rat with different pathophysiologies; they required injection or implantation of neoplastic cells into orthotopic locations, bones or the left ventricle of the heart. Several specific strains of rat have an increased incidence of spontaneous tumors. Carcinomas can be induced by either chemicals or physical agents. However, the most used and convenient way to induce bone metastases is a syngeneic transmission. MAT-Ly-Lu cells have been used in several models using Copenhagen rats to induce osteoblastic bone lesions. PA-III cells derived from Pollard tumors can also produce a combination of osteolytic and osteoblastic reactions at the site of transplantation. Osteolytic bone lesions can be obtained with an injection of Walker cells. The use of 13762 or c-SST2 cells allows also leads to osteolysis. Human xenografts can only be used in nude animals. It is essential to validate and correctly interpret the lesions in several models of bone metastasis. No animal model is sufficient by itself to represent the clinical findings observed in humans. The use of models developed in different species should be more predictive and bring a beam of arguments for a better knowledge of pathophysiological and therapeutic mechanisms.

摘要

骨转移在晚期乳腺癌或前列腺癌患者中很常见。骨转移主要可以是溶骨性、成骨性或混合性的。动物模型研究有助于在理解骨转移分子基础方面取得进展,并为治疗提供新靶点。已在大鼠中开发了几种具有不同病理生理学的动物模型;它们需要将肿瘤细胞注射或植入原位、骨骼或心脏左心室。几种特定品系的大鼠自发肿瘤发生率增加。癌可以由化学物质或物理因素诱导产生。然而,诱导骨转移最常用且方便的方法是同基因转移。MAT-Ly-Lu细胞已在使用哥本哈根大鼠的几种模型中用于诱导成骨性骨病变。源自波拉德肿瘤的PA-III细胞在移植部位也可产生溶骨和成骨反应的组合。注射沃克细胞可获得溶骨性骨病变。使用13762或c-SST2细胞也会导致骨溶解。人异种移植只能用于裸鼠。在几种骨转移模型中验证并正确解释病变至关重要。没有一种动物模型本身足以代表在人类中观察到的临床发现。使用在不同物种中开发的模型应该更具预测性,并为更好地了解病理生理和治疗机制提供一系列论据。

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