黑色素瘤细胞经常表达推测的癌症干细胞标志物,但这些标志物也存在于良性分化细胞中。
Putative Cancer Stem Cell Markers are Frequently Expressed by Melanoma Cells and but are also Present in Benign Differentiated Cells.
机构信息
Department of Internal Medicine II, University Hospital Tübingen, 72072 Tübingen, Germany.
Current Affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, Germany.
出版信息
Front Biosci (Landmark Ed). 2023 Sep 6;28(9):193. doi: 10.31083/j.fbl2809193.
BACKGROUND
Currently, there remains an incomplete view of cancer stem cells (CSCs) in solid tumours.
METHODS
We studied a panel of putative CSC surface markers (ALDH1A1, ABCG2, CD44v7/8, CD44v10, CD133, CD271, and Nestin) in 40 established melanoma cell lines and four early-passage melanoma strains by flow cytometry. We additionally examined 40 formalin-fixed paraffin-embedded melanoma tissues using immunofluorescence microscopy. This was compared with their expression in healthy skin, normal differentiated melanocytes and fibroblasts.
RESULTS
Most of the putative CSC markers were expressed by both melanoma cell lines and tissues. When present, these proteins were expressed by the majority of cells in the population. However, the expression of these markers by cells in healthy skin sections, normal differentiated melanocytes, and fibroblasts revealed that differentiated non-malignant cells also expressed CSC markers indicating that they lack of specificity for CSCs. Culturing cell lines under conditions more characteristic of the tumour microenvironment upregulated CSC marker expressions in a proportion of cell lines, which correlated with improved cell growth and viability.
CONCLUSIONS
The testing of melanoma cell lines (n = 40), early-passage cell strains (n = 4), and melanoma tissues (n = 40) showed that several putative CSC markers (ALDH1A1, ABCG2, CD44v7/8, CD44v10, CD133, CD271, and Nestin) are commonly present in a large proportion of melanoma cells and . Further, we showed that these putative markers lack specificity for CSCs because they are also expressed in differentiated non-malignant cell types (melanocytes, fibroblasts, and skin), which could limit their use as therapeutic targets. These data are consistent with the emerging notion of CSC plasticity and phenotype switching within cancer cell populations.
背景
目前,实体瘤中的癌症干细胞(CSC)仍然存在不完全的认识。
方法
我们通过流式细胞术研究了一组假定的 CSC 表面标志物(ALDH1A1、ABCG2、CD44v7/8、CD44v10、CD133、CD271 和 Nestin)在 40 种已建立的黑素瘤细胞系和四种早期传代黑素瘤株中的表达情况。我们还使用免疫荧光显微镜检查了 40 份福尔马林固定石蜡包埋的黑素瘤组织。将其与健康皮肤、正常分化的黑素细胞和成纤维细胞中的表达进行了比较。
结果
大多数假定的 CSC 标志物均在黑素瘤细胞系和组织中表达。当存在这些蛋白时,它们在群体中的大多数细胞中表达。然而,这些标志物在健康皮肤切片、正常分化的黑素细胞和成纤维细胞中的表达表明,分化的非恶性细胞也表达 CSC 标志物,这表明它们缺乏对 CSCs 的特异性。在更符合肿瘤微环境特征的条件下培养细胞系,可上调部分细胞系中 CSC 标志物的表达,这与细胞生长和活力的改善相关。
结论
对 40 种黑素瘤细胞系(n=40)、早期传代细胞株(n=4)和黑素瘤组织(n=40)的检测表明,几种假定的 CSC 标志物(ALDH1A1、ABCG2、CD44v7/8、CD44v10、CD133、CD271 和 Nestin)在很大一部分黑素瘤细胞中普遍存在。此外,我们表明这些假定的标志物缺乏对 CSCs 的特异性,因为它们也在分化的非恶性细胞类型(黑素细胞、成纤维细胞和皮肤)中表达,这可能限制了它们作为治疗靶点的应用。这些数据与癌症细胞群体中 CSC 可塑性和表型转换的新观点一致。