Role of COX-2 in tumorospheres derived from a breast cancer cell line.
Role of COX-2 in tumorospheres derived from a breast cancer cell line.
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DOI：
10.1016/j.jss.2010.03.003
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发表时间：
2011-06-01
期刊：
影响因子：
--
通讯作者：
Lucci A
中科院分区：
文献类型：
--
作者：
Singh B;Cook KR;Vincent L;Hall CS;Martin C;Lucci A
原发性乳腺癌中环氧合酶-2（考克斯-2）的表达预示着肿瘤细胞向骨髓的扩散，这是复发和远处转移的危险因素。“干细胞样”表型在肿瘤转移中可能是重要的。为了研究考克斯-2蛋白在乳腺癌干细胞样细胞中的作用，我们在来自MCF 7雌激素受体阳性乳腺癌细胞系的肿瘤球中通过共免疫荧光对其进行了分析。为了评价考克斯-2功能，我们在用肿瘤球衍生细胞进行的克隆形成试验中使用了考克斯-2抑制剂。我们在肿瘤球中检测到极高考克斯-2表达（考克斯-2 high）的罕见细胞（每个肿瘤球一个细胞）。考克斯-2转染的MCF 7细胞能够产生长期的肿瘤球培养，即使转染效率仅为百万分之一。我们在部分考克斯-2 high细胞中检测到OCT 4的表达，支持这些细胞可能是肿瘤干细胞样细胞的假设。重要的是，考克斯-2 high细胞显示Ki-67表达低于邻近细胞，表明考克斯-2 high细胞可能是肿瘤球的祖细胞。塞来昔布抑制肿瘤球培养物的生长和肿瘤球衍生细胞体外形成集落的能力，表明考克斯-2在这些过程中发挥积极作用。然而，2 μM塞来昔布未能根除肿瘤球起始细胞。最后，我们在含血清培养基中的塑料上生长的SUM 149炎性乳腺癌细胞中检测到罕见的考克斯-2高细胞; SUM 149细胞系产生非常高水平的考克斯-2蛋白。我们的研究结果支持考克斯-2在干细胞样乳腺癌细胞中的作用，并提示考克斯-2在播散性肿瘤细胞中的作用机制，已知播散性肿瘤细胞表现出干细胞样细胞的特征性生物标志物和功能特性。
Cyclooxygenase-2 (COX-2) expression in primary breast cancer predicts tumor cell dissemination to bone marrow, which is a risk factor for recurrence and distant metastasis. “Stem-like” phenotype may be important in cancer metastasis. To investigate the role of COX-2 protein in breast cancer stem-like cells we analyzed it by co-immunofluorescence in tumorospheres derived from the MCF7 estrogen receptor-positive breast cancer cell line. To evaluate COX-2 function we utilized a COX-2 inhibitor in a clonogenicity assay performed with tumorospheres-derived cells. We detected rare cells in tumorospheres (one cell per tumorosphere) with very high COX-2 expression (COX-2high). COX-2 transfected MCF7 cells were able to generate long-term tumorospheres culture, even though transfection efficiency was only one in a million cells. We detected expression of OCT4 in some COX-2high cells, supporting the hypothesis that these cells could be cancer stem-like cells. It is important that COX-2high cells showed less expression of Ki-67 than did neighboring cells, indicating that COX-2high cells may be progenitors of tumorospheres. Celecoxib inhibited the growth of tumorosphere cultures and the ability of tumorosphere-derived cells to form colonies in vitro, indicating an active role of COX-2 in these processes. However, 2 μM celecoxib failed to eradicate tumorosphere-initiating cells. Finally, we detected rare COX-2high cells among SUM149 inflammatory breast cancer cells growing on plastic in serum-containing medium; the SUM149 cell line produces a very high level of COX-2 protein. Our results support a role for COX-2 in stem-like breast cancer cells and suggest a mechanism behind a role for COX-2 in disseminated tumor cells, which are known to exhibit characteristic biomarkers and functional properties of stem-like cells.
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影响因子：
50.3
作者：
Crawford, YG;Gauthier, ML;Tlsty, TD
通讯作者：
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影响因子：
10.5
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64.5
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