Animal experimental systems are particularly useful for the study of human breast cancer. An ideal model shoulcl be easy to use, closely mimicking human physiopathology and has a stable tumor morbidity. The cell line ...Animal experimental systems are particularly useful for the study of human breast cancer. An ideal model shoulcl be easy to use, closely mimicking human physiopathology and has a stable tumor morbidity. The cell line MA891 was established from a spontaneous TA2 mouse mammary carcinoma by Cancer Institute of Chinese Academy of Medical Sciences. 3 Some researches indicated that MA891 had a very low immunogenecity and maintained a high metastatic potential in vivo. So it has been used as a better grafted mouse tumor model for studying cancer physiopathology and metastasis in human for years. However, about the biological characteristic and the histopathologic feature of this model there has been a lack of investigations.展开更多
Background A satisfactory animal model of breast cancer metastasizing to bone is unavailable. In this study, we used human breast cancer stem-like cells and human bone to build a novel “human-source” model of human ...Background A satisfactory animal model of breast cancer metastasizing to bone is unavailable. In this study, we used human breast cancer stem-like cells and human bone to build a novel “human-source” model of human breast cancer skeletal metastasis. Methods Human breast cancer stem-like cells, the CD44^＋/CD24^-/lower subpopulation, was separated and cultured. Before injection with the stem-like cells, mice were implanted with human bone in the right or left dorsal flanks. Animals in Groups A, B, and C were injected with 1×10^5, 1×10^6 human breast cancer stem-like cells, and 1×10^6 parental MDA-MB-231 cells, respectively. A positive control group （D） without implantation of human bone was also injected with 1×10^6 MDA-MB-231 cells. Immunohistochemistry was performed for determination of CD34, CD105, smooth muscle antibody, CD44, CD24, cytokine, CXC chemokine receptor-4 （CXCR4）, and osteopontin （OPN）. mRNA levels of CD44, CD24, CXCR4, and OPN in bone metastasis tissues were analyzed by real-time quantitative polymerase chain reaction （PCR）.Results Our results demonstrated that cells in implanted human bones of group B, which received 1×10^6 cancer stem-like cells, stained strongly positive for CD44, CXCR4, and OPN, whereas those of other groups showed no or minimum staining. Moreover, group B had the highest incidence of human bone metastasis （77.8%, P=0.0230） and no accompaniment of other tissue metastasis. The real-time PCR showed an increase of CD44, CXCR4, and OPN mRNA in metastatic bone tissues in group B compared with those of groups C and D, however the expression of CD24 mRNA in group B were the lowest. Conclusions In the novel “human source” model of breast cancer, breast cancer stem-like cells demonstrated a higher human bone-seeking ability. Its mechanism might be related to the higher expressions of CD44, CXCR4, and OPN, and the lower expression of CD24 in breast cancer stem-like cells.展开更多
目的用乳腺癌细胞MDA-MB-231建立一种有效简单的裸鼠乳腺癌动物模型。方法将5周龄雌性BALB/C裸鼠20只随机分为2组,即原位种植组,将0.1 m L MDA-MB-231乳腺癌细胞悬液种植于裸鼠右侧第2对乳腺脂肪垫;皮下种植组,将0.1 m L MDA-MB-231乳...目的用乳腺癌细胞MDA-MB-231建立一种有效简单的裸鼠乳腺癌动物模型。方法将5周龄雌性BALB/C裸鼠20只随机分为2组,即原位种植组,将0.1 m L MDA-MB-231乳腺癌细胞悬液种植于裸鼠右侧第2对乳腺脂肪垫;皮下种植组,将0.1 m L MDA-MB-231乳腺癌细胞悬液种植于裸鼠右侧胸部皮下。待裸鼠成瘤后,通过大体观察、超声观察肿瘤基本情况,记录肿瘤成瘤率、成瘤时间、肿瘤大小、体积、肿瘤开始坏死时间,绘制肿瘤生长曲线,接种后第8周解剖裸鼠、切取肿瘤块进行病理检查。结果原位种植组裸鼠成瘤率80%(8/10),皮下种植组裸鼠成瘤率90%(9/10),两者差异无统计学意义(P>0.05);原位种植组肿瘤块开始坏死时间晚于皮下种植组(P<0.05);原位种植组的肿瘤体积小于皮下种植组(P<0.05);超声观察显示皮下种植组肿瘤块血流少于原位种植组;病理学诊断2组肿瘤块均为浸润性导管癌。结论原位种植乳腺癌细胞MDA-MB-231建立的裸鼠乳腺癌模型,具有肿瘤生长缓慢、坏死发生晚、血供良好的优点,为探索乳腺癌的发病机制、治疗、转移、预防提供重要工具。展开更多
文摘Animal experimental systems are particularly useful for the study of human breast cancer. An ideal model shoulcl be easy to use, closely mimicking human physiopathology and has a stable tumor morbidity. The cell line MA891 was established from a spontaneous TA2 mouse mammary carcinoma by Cancer Institute of Chinese Academy of Medical Sciences. 3 Some researches indicated that MA891 had a very low immunogenecity and maintained a high metastatic potential in vivo. So it has been used as a better grafted mouse tumor model for studying cancer physiopathology and metastasis in human for years. However, about the biological characteristic and the histopathologic feature of this model there has been a lack of investigations.
基金This work was supported by grants from National Natural Science Foundation of China （No. 300740076）, Jiangsu Six Kinds of Outstanding Talents Foundation （No. 2006B070）, Jiangsu Science and Education for Health Foundation （No. RC2007054） and Jiangsu Province Post-doctor Foundation （No. 0601048B）.
文摘Background A satisfactory animal model of breast cancer metastasizing to bone is unavailable. In this study, we used human breast cancer stem-like cells and human bone to build a novel “human-source” model of human breast cancer skeletal metastasis. Methods Human breast cancer stem-like cells, the CD44^＋/CD24^-/lower subpopulation, was separated and cultured. Before injection with the stem-like cells, mice were implanted with human bone in the right or left dorsal flanks. Animals in Groups A, B, and C were injected with 1×10^5, 1×10^6 human breast cancer stem-like cells, and 1×10^6 parental MDA-MB-231 cells, respectively. A positive control group （D） without implantation of human bone was also injected with 1×10^6 MDA-MB-231 cells. Immunohistochemistry was performed for determination of CD34, CD105, smooth muscle antibody, CD44, CD24, cytokine, CXC chemokine receptor-4 （CXCR4）, and osteopontin （OPN）. mRNA levels of CD44, CD24, CXCR4, and OPN in bone metastasis tissues were analyzed by real-time quantitative polymerase chain reaction （PCR）.Results Our results demonstrated that cells in implanted human bones of group B, which received 1×10^6 cancer stem-like cells, stained strongly positive for CD44, CXCR4, and OPN, whereas those of other groups showed no or minimum staining. Moreover, group B had the highest incidence of human bone metastasis （77.8%, P=0.0230） and no accompaniment of other tissue metastasis. The real-time PCR showed an increase of CD44, CXCR4, and OPN mRNA in metastatic bone tissues in group B compared with those of groups C and D, however the expression of CD24 mRNA in group B were the lowest. Conclusions In the novel “human source” model of breast cancer, breast cancer stem-like cells demonstrated a higher human bone-seeking ability. Its mechanism might be related to the higher expressions of CD44, CXCR4, and OPN, and the lower expression of CD24 in breast cancer stem-like cells.
文摘目的用乳腺癌细胞MDA-MB-231建立一种有效简单的裸鼠乳腺癌动物模型。方法将5周龄雌性BALB/C裸鼠20只随机分为2组,即原位种植组,将0.1 m L MDA-MB-231乳腺癌细胞悬液种植于裸鼠右侧第2对乳腺脂肪垫;皮下种植组,将0.1 m L MDA-MB-231乳腺癌细胞悬液种植于裸鼠右侧胸部皮下。待裸鼠成瘤后,通过大体观察、超声观察肿瘤基本情况,记录肿瘤成瘤率、成瘤时间、肿瘤大小、体积、肿瘤开始坏死时间,绘制肿瘤生长曲线,接种后第8周解剖裸鼠、切取肿瘤块进行病理检查。结果原位种植组裸鼠成瘤率80%(8/10),皮下种植组裸鼠成瘤率90%(9/10),两者差异无统计学意义(P>0.05);原位种植组肿瘤块开始坏死时间晚于皮下种植组(P<0.05);原位种植组的肿瘤体积小于皮下种植组(P<0.05);超声观察显示皮下种植组肿瘤块血流少于原位种植组;病理学诊断2组肿瘤块均为浸润性导管癌。结论原位种植乳腺癌细胞MDA-MB-231建立的裸鼠乳腺癌模型,具有肿瘤生长缓慢、坏死发生晚、血供良好的优点,为探索乳腺癌的发病机制、治疗、转移、预防提供重要工具。
