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TAp63 and ΔNp63 (p40) in prostate adenocarcinomas: ΔNp63 associates with a basal-like cancer stem cell population but not with metastasis
Virchows Archiv ( IF 3.5 ) Pub Date : 2020-10-10 , DOI: 10.1007/s00428-020-02944-z
Michaela Galoczova , Rudolf Nenutil , Zuzana Pokorna , Borivoj Vojtesek , Philip J. Coates

Like other malignancies, prostate tumors are thought to contain cancer stem-like cells (CSCs) that are responsible for growth, metastasis, and therapy resistance. ΔNp63 (also called p40) is a regulator of normal prostate stem/progenitor cell activities and a marker of normal basal epithelial cells. The levels of ΔNp63 are reduced in prostate adenocarcinomas, although there is also evidence that ΔNp63 is involved in CSC regulation and drives metastasis to the bone. We studied metastatic deposits of prostate cancers with isoform-specific ΔNp63 and TAp63 antibodies. We identified p63-positive cells in only 3 of 42 metastatic prostate tumors (7%), including 2/38 (5.3%) “usual-type” adenocarcinomas. ΔNp63 and TAp63 isoforms were present in the nuclei of a small subpopulation (< 1%) of tumor cells in these metastases. ΔNp63-positive cells showed a basal-like cell phenotype (cytokeratin 8- and androgen receptor-negative, high molecular weight cytokeratin- and cytokeratin 19-positive), distinct from the tumor bulk. TAp63-positive cells were similar but were sometimes cytokeratin 8-positive. A subset of ΔNp63-positive tumor cells were CD44-positive, a marker of “basal” CSCs but were not positive for the “epithelial” CSC marker ALDH1. TAp63 was not associated with either of these CSC markers. None of the tumors containing p63-positive cells showed evidence of bone metastasis, compared with 28% of the p63-negative tumors. These data show that both ΔNp63 and TAp63 are present in only a small proportion of prostate adenocarcinomas and do not associate with metastasis. The data suggest heterogeneity of CSCs in prostate cancer, similar to other cancer types.



中文翻译:

前列腺腺癌中的TAp63和ΔNp63(p40):ΔNp63与基底样癌干细胞群体相关,但与转移无关

像其他恶性肿瘤一样,前列腺肿瘤也被认为含有癌干样细胞(CSC),它们负责生长,转移和治疗耐药性。ΔNp63(也称为p40)是正常前列腺干/祖细胞活性的调节剂,也是正常基础上皮细胞的标志物。前列腺腺癌中ΔNp63的水平降低,尽管也有证据表明ΔNp63参与CSC调节并推动转移至骨骼。我们用同工型特异性ΔNp63和TAp63抗体研究了前列腺癌的转移性沉积物。我们在42例转移性前列腺肿瘤中仅3例(7%)鉴定出p63阳性细胞,包括2/38(5.3%)“常规型”腺癌。在这些转移中,一小部分亚群(<1%)的肿瘤细胞核中存在ΔNp63和TAp63亚型。ΔNp63阳性细胞表现出基底样细胞表型(细胞角蛋白8和雄激素受体阴性,高分子量细胞角蛋白和细胞角蛋白19阳性),与肿瘤体积不同。TAp63阳性细胞相似,但有时细胞角蛋白8阳性。ΔNp63阳性肿瘤细胞的一部分是CD44阳性,这是“基础” CSC的标志物,但对“上皮” CSC标志物ALDH1却不是阳性。TAp63与这些CSC标记均不相关。包含p63阳性细胞的肿瘤均未显示出骨转移的证据,而p63阴性肿瘤为28%。这些数据表明,ΔNp63和TAp63都仅存在于一小部分前列腺腺癌中,并且与转移无关。数据表明前列腺癌中CSC的异质性,与其他类型的癌症相似。

更新日期:2020-10-11
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