Establishment of a nude mouse transplantable model of a human malignant fibrous histiocytoma of the mandible with high metastatic potential to the lung
Establishment of a nude mouse transplantable model of a human malignant fibrous histiocytoma of the mandible with high metastatic potential to the lung
复制标题
人下颌骨高肺转移恶性纤维组织细胞瘤裸鼠移植模型的建立
DOI：
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发表时间：
2008
影响因子：
3.6
通讯作者：
M. Urade
中科院分区：
文献类型：
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作者：
Tsunenari Maeda;S. Hashitani;Yusuke Zushi;Emi Segawa;N. Tanaka;K. Sakurai;M. Urade
恶性纤维组织细胞瘤(MFH)是发生于骨和软组织的最高级别肉瘤之一。由于化疗耐药和对各种器官的高转移潜能，其预后很差。很少有下颌或口腔MFH的病例被记录在案。我们建立了人下颌骨MFH的裸鼠肿瘤细胞系(MFH-N)，并对其特性进行了研究。组织学上，MFH-N与原始肿瘤相同，呈多形性，但转移潜能较低。免疫组织化学显示，原发瘤和异种瘤均表达波形蛋白、S-100、α-SMA和组织细胞标志物CD68。溶菌酶在原始肿瘤中有表达，但在移植瘤中仅有零星表达。逆转录-聚合酶链式反应分析表明，该肿瘤系中含有人β-肌动蛋白，表明该肿瘤来源于人类。在一项平行实验中，我们从MFH-N建立了一个新的MFH-NC细胞系。接种于裸鼠两侧和颌下区的肿瘤细胞在组织学上与MFH-N和原始肿瘤相似；接种后约5个月发现多处肺转移。Western blotting结果显示，MFH-N和MFH-NC中各种转移相关分子的表达水平存在差异。在MFH-NC中，MMP7、MMP9、MT1-MMP4、CXCR4、COX-2和整合素α4的表达上调，而MMP2和TIMP1的表达下调。两株细胞均未检测到TIMP2、整合素αL和唾液酸化刘易斯X的表达。结果表明，可移植于裸鼠体内的MFH-N肿瘤细胞系是研究MFH生物学行为的有用模型。
Malignant fibrous histiocytoma (MFH) is one of the highest-grade sarcomas arising in bone and soft tissue. Its prognosis is poor because of chemoresistance and high metastatic potential to various organs. Few cases arising of MFH of the mandible or oral cavity have been documented. We established a tumor line in nude mice (MFH-N), which was derived from human MFH of the mandible and examined the characteristics of this tumor line. Histologically, MFH-N was identical to the original tumor and showed a storiform-pleomorphic pattern, but had low metastatic potential. Immunohistochemically, both the original and xenografted tumors expressed vimentin, S-100, α-SMA, and histiocytic marker CD68. Lysozyme was expressed by the original tumor, but only sporadically by the xenografted tumor. RT-PCR analysis demonstrated human β-actin in this tumor line, indicating the human origin. In a parallel experiment, we established a new MFH cell line (MFH-NC) from MFH-N. Tumor cells inoculated into the flanks and submandibular region of nude mice developed into tumors histologically similar to MFH-N and the original tumor; multiple lung metastases were detected approximately 5 months after inoculation. The expression levels of various metastasis-related molecules differed between MFH-N and MFH-NC on Western blotting. In MFH-NC, the expressions of MMP7, MMP9, MT1-MMP, CXCR4, COX-2 and integrin α4 were up-regulated, while those of MMP2 and TIMP1 were down-regulated. Expression of TIMP2, integrinαL and sialyl lewis X were not detected in either line. Our findings suggest that the MFH-N tumor line transplantable in nude mice is a useful model for studying the biological behavior of MFH.
影响因子：
11.2
作者：
J. Rheinwald;M. Beckett
通讯作者：
J. Rheinwald;M. Beckett