Orthotopic non-metastatic and metastatic oral cancer mouse models.
Orthotopic non-metastatic and metastatic oral cancer mouse models.
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原位非转移性和转移性口腔癌小鼠模型。
DOI：
10.1016/j.oraloncology.2015.01.012
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发表时间：
2015-05
期刊：
影响因子：
4.8
通讯作者：
Trackman, Philip C.
中科院分区：
文献类型：
--
作者：
Bais, Manish V.;Kukuruzinska, Maria;Trackman, Philip C.
口腔癌的特点是发病率和死亡率高，易于转移到不同的组织，包括肺、肝和骨。尽管在理解口腔癌的突变谱和失调途径方面取得了进展，但在过去几十年中，患者的生存率并没有显着提高。因此，需要建立再现人口腔癌转移的体内模型以评估新药物的治疗潜力。在这里，我们报告原位舌癌裸鼠模型研究口腔癌的生长和转移，分别使用人转移（UMSCC 2）和非转移（CAL 27）细胞系。用表达红色荧光蛋白（DsRed）的慢病毒转导这些细胞系，然后注射到免疫缺陷小鼠的舌中，产生原位舌肿瘤，可以通过用体内成像系统（IVIS 200）进行荧光测量来监测其生长和转移。在第15天后，CAL 27-DsRed诱导的肿瘤的生长速率高于UMSCC 2-DsRed肿瘤，而UMSCC 2-DsRed肿瘤在第21天开始显示转移。重要的是，UMSCC 2肿瘤转移到许多组织，包括颌下腺、肺、肾、肝和骨。此外，对CAL 27和UMSCC 2细胞诱导的舌肿瘤的免疫组织化学分析显示，人类癌症中失调的促肿瘤发生途径的组分表达升高，包括细胞周期蛋白D1、PCNA、Ki-67、LSD 1、LOXL 2、MT-MMP 1、DPAGT 1、E-钙粘蛋白、OCT 4A和H3 K4 me 1/2。这些原位小鼠模型可能是有用的工具，用于深入了解新型口腔癌候选药物的活性和机制。
Oral cancer is characterized by high morbidity and mortality with a predisposition to metastasize to different tissues, including lung, liver, and bone. Despite progress in the understanding of mutational profiles and deregulated pathways in oral cancer, patient survival has not significantly improved over the past decades. Therefore, there is a need to establish in vivo models that recapitulate human oral cancer metastasis to evaluate therapeutic potential of novel drugs. Here we report orthotopic tongue cancer nude mouse models to study oral cancer growth and metastasis using human metastatic (UMSCC2) and non-metastatic (CAL27) cell lines, respectively. Transduction of these cell lines with lentivirus expressing red fluorescent protein (DsRed) followed by injection into tongues of immunodeficient mice generated orthotopic tongue tumors that could be monitored for growth and metastasis by fluorescence measurement with an in vivo Imaging System (IVIS 200). The growth rates of CAL27-DsRed induced tumors were higher than UMSCC2-DsRed tumors after day 15, while UMSCC2-DsRed tumors revealed metastasis beginning on day 21. Importantly, UMSCC2 tumors metastasized to a number of tissues including the submandibular gland, lung, kidney, liver, and bone. Further, immunohistochemical analyses of tongue tumors induced by CAL27 and UMSCC2 cells revealed elevated expression of components of protumorigenic pathways deregulated in human cancers, including Cyclin D1, PCNA, Ki-67, LSD1, LOXL2, MT-MMP1, DPAGT1, E-cadherin, OCT4A, and H3K4me1/2. These orthotopic mouse models are likely to be useful tools for gaining insights into the activity and mechanisms of novel oral cancer drug candidates.
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影响因子：
8.8
作者：
Akanuma, N.;Hoshino, I.;Akutsu, Y.;Murakami, K.;Isozaki, Y.;Maruyama, T.;Yusup, G.;Qin, W.;Toyozumi, T.;Takahashi, M.;Suito, H.;Hu, X.;Sekino, N.;Matsubara, H.
通讯作者：
Matsubara, H.
影响因子：
4.1
作者：
Bais, M. V.;Wigner, N.;Young, M.;Toholka, R.;Graves, D. T.;Morgan, E. F.;Gerstenfeld, L. C.;Einhorn, T. A.
通讯作者：
Einhorn, T. A.
DOI：
10.1002/hed.2880160506
发表时间：
1994-09-01
影响因子：
2.9
作者：
HAWKINS, BL;HENIFORD, BW;HENDLER, FJ
通讯作者：
HENDLER, FJ
影响因子：
3
作者：
Kim S
通讯作者：
Kim S
影响因子：
15.9
作者：
Rothenberg, S. Michael;Ellisen, Leif W.
通讯作者：
Ellisen, Leif W.