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A novel mouse model of human breast cancer stem-like cells with high CD44^＋CD24^–/lower phenotype metastasis to human bone

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Chinese Medical Journal 2008年第20期121卷 1980-1986页

作者： LING Li-jun WANG Shui LIU Xiao-an SHEN En-chao DING Qiang LU Chao XU Jian CAO Qin-hong ZHU Hai-qing WANG Feng Department of General Surgery First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu 210029 China Department of Pathology Nanjing Brain Hospital Affiliated to Nanjing Medical University Nanjing Jiangsu 210029 China Department of Nuclear Medicine First Nanjing Hospital Affiliated to Nanjing Medical University Nanjing Jiangsu 210006 China

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.

关键词： breast cancer cancer stem-like cells human source bone metastasis animal model

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A novel mouse model of human breast cancer stem-like cells with high CD44+CD24-/lower phenotype metastasis to human bone

A novel mouse model of human breast cancer stem-like cells w...

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第十一届全国中医及中西医结合乳腺病学术会议

作者： LING Li-jun,WANG Shui,LIU Xiao-an,SHEN En-chao,DING Qiang,LU Chao,XU Jian,CAO Qin-hong, ZHU Hai-qing and WANG Feng Department of General Surgery,First Affiliated Hospital of NJMU(Nanjing Medical University),Nanjing, Jiangsu 210029,China Department of Pathology,Nanjing Brain Hospital Affiliated to NJMU(Nanjing Medical University),Nanjing, Jiangsu 210029,China Department of Nuclear Medicine,First Nanjing Hospital Affiliated to NJMU(Nanjing Medical University), Nanjing,Jiangsu 210029,China

Background A satisfactory animal model that avoids species-specific factors and simultaneously shares similari ties to the clinical pathophysiological progression of breast cancer metastasizing to bone is unavailable.A subpopulation(CD44/CD24)of breast cancer cells possesses stem/progenitor cell properties(cancer stem-like cell).CD44 potentiates the adherence of metastatic breast cancer cells to bone marrow endothelial *** the present study,we used hepatocyte growth factor to enhance the proportion of CD44/CD24 subpopulation in the human breast cancer cell line *** used these human breast cancer stem-like cells and implantation of human bone to build a novel"human-source"model of human breast cancer skeletal metastasis.

关键词： breast cancer cancer stem-like cells human source bone metastasis animal model

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