Imagable 4T1 model for the study of late stage breast cancer.
Imagable 4T1 model for the study of late stage breast cancer.
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DOI：
10.1186/1471-2407-8-228
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发表时间：
2008-08-09
期刊：
影响因子：
3.8
通讯作者：
Sahagian GG
中科院分区：
文献类型：
--
作者：
Tao K;Fang M;Alroy J;Sahagian GG
4T1小鼠乳腺肿瘤细胞系是少数几种能够有效转移到人类乳腺癌受影响部位的乳腺癌模型之一。在这里，我们描述了两个经过修饰的4T1细胞系，以便于分析肿瘤生长和转移以及评估基因在体内的功能。本文报道了先天性免疫和获得性免疫参与转移的新信息，以及该模型在晚期乳腺癌研究中使用相关的其他特征。这些细胞系被设计为萤火虫荧光素酶的稳定表达，以便在体内跟踪和定量细胞。生物光子成像用于表征细胞系在体内的生长和转移，改进的基因表达方法用于表征观察到的转移表型的基础。原发部位的细胞呈双相生长，在细胞导入后5-6周的第二生长期检测到转移。生长消退，发生在第3-4周，伴有广泛的坏死和白细胞浸润。在BALB/c SCID小鼠中未发生双相肿瘤生长，表明该效应涉及获得性免疫反应。在第2周观察到脾脏和肝脏的造血和循环白细胞水平升高，并逐渐增加，直到第6-8周死亡。基因表达分析显示，集落刺激因子、细胞因子和趋化因子、急性期蛋白、血管生成因子和ECM修饰蛋白等多种分泌因子与4T1转移表型相关。还确定了可能负责产生这些因子的信号通路。刺激血管生成和ECM修饰以及诱导造血、白细胞募集和活化的因子的产生表明，4T1肿瘤细胞在协调有利于肿瘤细胞传播和转移的肿瘤环境变化方面发挥着比以前所认识的更直接的作用。新的细胞系将极大地促进晚期乳腺癌的研究和癌症药物和其他治疗方法的临床前评估，特别是那些靶向免疫系统对肿瘤转移的影响。
The 4T1 mouse mammary tumor cell line is one of only a few breast cancer models with the capacity to metastasize efficiently to sites affected in human breast cancer. Here we describe two 4T1 cell lines modified to facilitate analysis of tumor growth and metastasis and evaluation of gene function in vivo. New information regarding the involvement of innate and acquired immunity in metastasis and other characteristics of the model relevant to its use in the study of late stage breast cancer are reported. The lines were engineered for stable expression of firefly luciferase to allow tracking and quantitation of the cells in vivo. Biophotonic imaging was used to characterize growth and metastasis of the lines in vivo and an improved gene expression approach was used to characterize the basis for the metastatic phenotype that was observed. Growth of cells at the primary site was biphasic with metastasis detected during the second growth phase 5–6 weeks after introduction of the cells. Regression of growth, which occurred in weeks 3–4, was associated with extensive necrosis and infiltration of leukocytes. Biphasic tumor growth did not occur in BALB/c SCID mice indicating involvement of an acquired immune response in the effect. Hematopoiesis in spleen and liver and elevated levels of circulating leukocytes were observed at week 2 and increased progressively until death at week 6–8. Gene expression analysis revealed an association of several secreted factors including colony stimulatory factors, cytokines and chemokines, acute phase proteins, angiogenesis factors and ECM modifying proteins with the 4T1 metastatic phenotype. Signaling pathways likely to be responsible for production of these factors were also identified. The production of factors that stimulate angiogenesis and ECM modification and induce hematopoiesis, recruitment and activation of leukocytes suggest that 4T1 tumor cells play a more direct role than previously appreciated in orchestrating changes in the tumor environment conducive to tumor cell dissemination and metastasis. The new cell lines will greatly facilitate the study of late stage breast and preclinical assessment of cancer drugs and other therapeutics particularly those targeting immune system effects on tumor metastasis.
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影响因子：
7
作者：
Kuhn, K;Baker, SC;Chee, MS
通讯作者：
Chee, MS
DOI：
10.1111/j.1365-2613.2007.00539.x
发表时间：
2007-10-01
影响因子：
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作者：
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