Lipid Droplets: A New Player in Colorectal Cancer Stem Cells Unveiled by Spectroscopic Imaging

Author:

Tirinato Luca12,Liberale Carlo34,Di Franco Simone56,Candeloro Patrizio2,Benfante Antonina5,La Rocca Rosanna4,Potze Lisette6,Marotta Roberto7,Ruffilli Roberta7,Rajamanickam Vijayakumar P.34,Malerba Mario4,De Angelis Francesco4,Falqui Andrea37,Carbone Ennio89,Todaro Matilde5,Medema Jan Paul6,Stassi Giorgio5,Di Fabrizio Enzo123

Affiliation:

1. PSE Division King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia

2. BioNEM Lab, Department of Experimental and Clinical Medicine University Magna Graecia of Catanzaro, Catanzaro, Italy

3. BESE Division King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia

4. Nanostructures and Istituto Italiano di Tecnologia, Genova, Italy

5. Cellular and Molecular Pathophysiology Laboratory, Department of Surgical and Oncological Sciences University of Palermo, Palermo, Italy

6. Laboratory for Experimental Oncology and Radiology (LEXOR) Center for Experimental Molecular Medicine (CEMM), Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands

7. Nanochemistry Istituto Italiano di Tecnologia, Genova, Italy

8. Department of Microbiology Tumor and Cell Biology (MTC) Karolinska Institute, Stockholm, Sweden

9. Tumor Immunology Lab, Dipartimento di Medicina Sperimentale e Clinica Università Magna Graecia di Catanzaro, Catanzaro, Italy

Abstract

Abstract 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. Stem Cells  2015;33:35–44

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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