Abstract
Cancer stem cells (CSCs) are thought to drive tumor growth, metastasis and chemoresistance. Although surface markers such as CD133 and CD44 have been successfully used to isolate CSCs, their expression is not exclusively linked to the CSC phenotype and is prone to environmental alteration. We identified cells with an autofluorescent subcellular compartment that exclusively showed CSC features across different human tumor types. Primary tumor-derived autofluorescent cells did not overlap with side-population (SP) cells, were enriched in sphere culture and during chemotherapy, strongly expressed pluripotency-associated genes, were highly metastatic and showed long-term in vivo tumorigenicity, even at the single-cell level. Autofluorescence was due to riboflavin accumulation in membrane-bounded cytoplasmic structures bearing ATP-dependent ABCG2 transporters. In summary, we identified and characterized an intrinsic autofluorescent phenotype in CSCs of diverse epithelial cancers and used this marker to isolate and characterize these cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters / metabolism
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Animals
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Autophagy
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Autophagy-Related Protein 12
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Biomarkers, Tumor / metabolism*
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Carcinoma, Hepatocellular / pathology
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Carcinoma, Non-Small-Cell Lung / pathology
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Carcinoma, Pancreatic Ductal / pathology
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Cell Separation / methods*
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Colorectal Neoplasms / pathology
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Female
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Humans
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Liver Neoplasms / pathology
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Lung Neoplasms / pathology
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Mice
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Mice, Nude
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Microtubule-Associated Proteins / biosynthesis
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Neoplasm Proteins / metabolism
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Neoplastic Stem Cells / metabolism*
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Neoplastic Stem Cells / pathology*
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Optical Imaging / methods*
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Pancreatic Neoplasms / pathology
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Riboflavin / metabolism*
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Small Ubiquitin-Related Modifier Proteins / biosynthesis
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Tumor Cells, Cultured
Substances
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ABCG2 protein, human
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ATG12 protein, human
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ATP Binding Cassette Transporter, Subfamily G, Member 2
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ATP-Binding Cassette Transporters
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Autophagy-Related Protein 12
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Biomarkers, Tumor
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MAP1LC3A protein, human
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Microtubule-Associated Proteins
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Neoplasm Proteins
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Small Ubiquitin-Related Modifier Proteins
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Riboflavin