Lenos Kristiaan J, Vermeulen Louis
Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Experimental Molecular Medicine (CEMM), Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands.
Ann Transl Med. 2016 Dec;4(24):519. doi: 10.21037/atm.2016.11.81.
A population of stem-like cells in tumors, the so-called cancer stem cells (CSCs), are being held responsible for therapy resistance and tumor recurrence. In analogy with normal stem cells, CSCs possess the capacity of long term self-renewal and multilineage differentiation. CSCs are believed to be more resistant to various therapies compared to their differentiated offspring and therefore the cause of tumor relapse. Markers for CSCs have been identified using xenograft transplantation assays and lineage tracing in mouse models, however the specificity and validity of many of these markers is under debate. Recently, low proteasome activity has been postulated as a novel CSC marker. In several solid malignancies a small subset of low proteasomal activity cells with CSC characteristics were identified, suggesting that proteasomal activity might be a functional marker for CSCs. In this perspective, we will discuss a recent study by Munakata ., describing a population of colorectal cancer cells with CSC properties, characterized by low proteasome activity and treatment resistance. We will put this finding in a broader view by discussing the challenges and issues inherent with CSC identification, as well as some emerging insights in the CSC concept.
肿瘤中的一类干细胞样细胞,即所谓的癌症干细胞(CSCs),被认为是导致治疗抵抗和肿瘤复发的原因。与正常干细胞类似,癌症干细胞具有长期自我更新和多谱系分化的能力。与它们分化后的子代细胞相比,癌症干细胞被认为对各种治疗更具抗性,因此是肿瘤复发的原因。通过异种移植实验和小鼠模型中的谱系追踪,已经鉴定出了癌症干细胞的标志物,然而其中许多标志物的特异性和有效性仍存在争议。最近,低蛋白酶体活性被假定为一种新的癌症干细胞标志物。在几种实体恶性肿瘤中,已鉴定出一小部分具有癌症干细胞特征的低蛋白酶体活性细胞,这表明蛋白酶体活性可能是癌症干细胞的一个功能性标志物。从这个角度出发,我们将讨论宗方等人最近的一项研究,该研究描述了一群具有癌症干细胞特性的结肠癌细胞,其特征为低蛋白酶体活性和治疗抗性。我们将通过讨论癌症干细胞识别中固有的挑战和问题,以及癌症干细胞概念中的一些新见解,将这一发现置于更广阔的视野中。