Tirinato Luca, Liberale Carlo, Di Franco Simone, Candeloro Patrizio, Benfante Antonina, La Rocca Rosanna, Potze Lisette, Marotta Roberto, Ruffilli Roberta, Rajamanickam Vijayakumar P, Malerba Mario, De Angelis Francesco, Falqui Andrea, Carbone Ennio, Todaro Matilde, Medema Jan Paul, Stassi Giorgio, Di Fabrizio Enzo
PSE Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia; BioNEM Lab, Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, Italy.
Stem Cells. 2015 Jan;33(1):35-44. doi: 10.1002/stem.1837.
The cancer stem cell (CSC) model is describing tumors as a hierarchical organized system and CSCs are suggested to be responsible for cancer recurrence after therapy. The identification of specific markers of CSCs is therefore of paramount importance. Here, we show that high levels of lipid droplets (LDs) are a distinctive mark of CSCs in colorectal (CR) cancer. This increased lipid content was clearly revealed by label-free Raman spectroscopy and it directly correlates with well-accepted CR-CSC markers as CD133 and Wnt pathway activity. By xenotransplantation experiments, we have finally demonstrated that CR-CSCs overexpressing LDs retain most tumorigenic potential. A relevant conceptual advance in this work is the demonstration that a cellular organelle, the LD, is a signature of CSCs, in addition to molecular markers. A further functional characterization of LDs could lead soon to design new target therapies against CR-CSCs.
癌症干细胞(CSC)模型将肿瘤描述为一个分层组织的系统,并且认为CSC是治疗后癌症复发的原因。因此,识别CSC的特定标志物至关重要。在此,我们表明高水平的脂滴(LDs)是结直肠癌(CR)中CSC的一个独特标志。无标记拉曼光谱清楚地揭示了这种增加的脂质含量,并且它与公认的CR-CSC标志物如CD133和Wnt信号通路活性直接相关。通过异种移植实验,我们最终证明了过表达LDs的CR-CSC保留了大部分致瘤潜力。这项工作的一个相关概念性进展是证明了一种细胞器——LD,除了分子标志物外,也是CSC的一个标志。对LDs的进一步功能表征可能很快会导致设计针对CR-CSC的新靶向疗法。