School of Medicine, University of Sheffield, Sheffield, UK.
Prostate. 2010 Jun 1;70(8):875-82. doi: 10.1002/pros.21121.
Tumour cells with a stem cell-like phenotype have recently been identified in prostate tumors and it has been suggested that this population may be responsible for the diversity of cell types within tumors and also for the initiation of metastases. These cells carry a number of defined markers: they are cd133 and cd44+ve and express high levels of alpha2beta1 integrin. In this study we have, for the first time, assessed matched primary and bone marrow biopsies from prostate cancer patients for the distribution of cells carrying these and a number of other putative stem cell markers.
Eleven matched (primary and bone metastasis) specimens from prostate cancer patients were assessed for the presence of cd133, cd44, alpha2beta1 integrin, CXCR4, c-met, alpha6 integrin, and nestin using immunohistochemistry and stain intensity and distribution scored.
In the bone metastases, tumor cells staining positively for cd133 were detected at low frequency in approximately 50% of samples. Staining for nestin was confined to endothelium. Positive staining of tumor cells for the other antigens was present at variable frequency in >70% of metastases with the exception of CXCR4 which was absent from all but 2 specimens. Where positive staining of tumor cells was present in the metastasis, cells staining for each antigen were present in the matched primary with the exception of cd44 which was absent in all but 2/11 matched primary tissues.
In established metastases no single or combination of marker expression profiles identify the established metastatic phenotype, although cd44 expression was shown to be more frequent in metastases that in primary cancers.
最近在前列腺肿瘤中发现了具有干细胞样表型的肿瘤细胞,有人提出,这种细胞群可能是肿瘤内细胞类型多样性的原因,也是转移的起始原因。这些细胞携带许多定义明确的标志物:它们是 cd133 和 cd44+ve,并表达高水平的 alpha2beta1 整合素。在这项研究中,我们首次评估了来自前列腺癌患者的匹配原发性和骨髓活检标本中携带这些标志物和其他一些假定干细胞标志物的细胞的分布。
使用免疫组织化学和染色强度和分布评分,评估来自前列腺癌患者的 11 个匹配(原发性和骨转移)标本中 cd133、cd44、alpha2beta1 整合素、CXCR4、c-met、alpha6 整合素和 nestin 的存在情况。
在骨转移中,cd133 阳性肿瘤细胞以低频率存在于约 50%的样本中。nestin 的染色仅限于内皮细胞。除 CXCR4 外,其他抗原的肿瘤细胞阳性染色在>70%的转移中以不同频率存在,但除 2 个标本外,CXCR4 在所有标本中均不存在。在转移中存在肿瘤细胞阳性染色的情况下,除 cd44 外,每个抗原的染色细胞均存在于匹配的原发性组织中,除 11 个匹配的原发性组织中的 2 个外,cd44 在所有标本中均不存在。
在已建立的转移中,没有单一或组合的标志物表达谱可以识别已建立的转移表型,尽管 cd44 表达在转移中比在原发性癌症中更常见。