Modeling Primary Bone Tumors and Bone Metastasis with Solid Tumor Graft Implantation into Bone.
Modeling Primary Bone Tumors and Bone Metastasis with Solid Tumor Graft Implantation into Bone.
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DOI：
10.3791/61313
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发表时间：
2020-09-09
期刊：
影响因子：
--
通讯作者：
Allen MJ
中科院分区：
文献类型：
--
作者：
Hildreth BE 3rd;Palmer C;Allen MJ
原发性骨肿瘤或实体瘤的骨转移导致疼痛的溶骨、成骨或溶骨/成骨混合病变。这些病变损害骨骼结构，增加病理性骨折的风险，并使患者的治疗选择有限。原发性骨肿瘤转移到远处器官，一些类型能够扩散到其他骨骼部位。然而，最近的证据表明，在许多实体瘤中，已经扩散到骨骼的癌细胞可能是最终转移到其他器官系统的细胞的主要来源。大多数同体或异种移植小鼠原发性骨肿瘤模型涉及骨内（原位）注射肿瘤细胞悬液。一些实体瘤骨骼转移的动物模型也依赖于直接骨注射，而另一些动物模型则试图通过血管内注射细胞或向原发肿瘤器官注射细胞来重现骨转移级联的其他步骤。然而，这些模型都不可靠地发生骨转移或发生率为100%。此外，直接骨内注射肿瘤细胞已被证明与潜在的肺肿瘤栓塞有关。这些栓塞性肿瘤细胞移植但不重现转移级联。我们报道了一种骨肉瘤小鼠模型，使用微创手术技术将新鲜或冷冻保存的肿瘤碎片（由肿瘤细胞和基质组成）直接植入胫骨近端。这些动物发生了可重复的植入、生长，并随着时间的推移发生骨溶解和肺转移。该技术具有多功能性，可用于模拟实体瘤骨转移，并且可以很容易地使用由一种或多种细胞类型、基因修饰细胞、患者来源的异种移植物和/或可通过光学或高级成像跟踪的标记细胞组成的移植物。在这里，我们展示了这种技术，用实体瘤移植物植入骨来模拟原发性骨肿瘤和骨转移。
Primary bone tumors or bone metastasis from solid tumors result in painful osteolytic, osteoblastic, or mixed osteolytic/osteoblastic lesions. These lesions compromise bone structure, increase the risk of pathologic fracture, and leave patients with limited treatment options. Primary bone tumors metastasize to distant organs, with some types capable of spreading to other skeletal sites. However, recent evidence suggests that with many solid tumors, cancer cells that have spread to bone may be the primary source of cells that ultimately metastasize to other organ systems. Most syngeneic or xenograft mouse models of primary bone tumors involve intra-osseous (orthotopic) injection of tumor cell suspensions. Some animal models of skeletal metastasis from solid tumors also depend on direct bone injection, while others attempt to recapitulate additional steps of the bone metastatic cascade by injecting cells intravascularly or into the organ of the primary tumor. However, none of these models develop bone metastasis reliably or with an incidence of 100%. In addition, direct intra-osseous injection of tumor cells has been shown to be associated with potential tumor embolization of the lung. These embolic tumor cells engraft but do not recapitulate the metastatic cascade. We reported a mouse model of osteosarcoma in which fresh or cryopreserved tumor fragments (consisting of tumor cells plus stroma) are implanted directly into the proximal tibia using a minimally invasive surgical technique. These animals developed reproducible engraftment, growth, and, over time, osteolysis and lung metastasis. This technique has the versatility to be used to model solid tumor bone metastasis and can readily employ grafts consisting of one or multiple cell types, genetically-modified cells, patient-derived xenografts, and/or labeled cells that can be tracked by optical or advanced imaging. Here, we demonstrate this technique, modeling primary bone tumors and bone metastasis using solid tumor graft implantation into bone.
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头颈鳞状细胞癌的免疫功能低下和免疫能力的小鼠模型。
影响因子：
4
作者：
Lei ZG;Ren XH;Wang SS;Liang XH;Tang YL
通讯作者：
Tang YL
DOI：
10.1038/bonekey.2016.4
发表时间：
2016-02-17
期刊：
BONEKEY REPORTS
影响因子：
--
作者：
Dai, Jinlu;Hensel, Janine;Shiozawa, Yusuke
通讯作者：
Shiozawa, Yusuke
影响因子：
8.8
作者：
James, JJ;Evans, AJ;Robertson, JFR
通讯作者：
Robertson, JFR
一种新型患者来源的骨转移性前列腺癌股骨内异种移植模型，再现了混合的溶骨性和成骨性病变。
影响因子：
7.4
作者：
Raheem O;Kulidjian AA;Wu C;Jeong YB;Yamaguchi T;Smith KM;Goff D;Leu H;Morris SR;Cacalano NA;Masuda K;Jamieson CH;Kane CJ;Jamieson CA
通讯作者：
Jamieson CA
影响因子：
7.4
作者：
Lefley, Diane;Howard, Faith;Ottewell, Penelope
通讯作者：
Ottewell, Penelope