TY - JOUR
T1 - Intracellular autofluorescence
T2 - A biomarker for epithelial cancer stem cells
AU - Miranda-Lorenzo, Irene
AU - Dorado, Jorge
AU - Lonardo, Enza
AU - Alcala, Sonia
AU - Serrano, Alicia G.
AU - Clausell-Tormos, Jenifer
AU - Cioffi, Michele
AU - Megias, Diego
AU - Zagorac, Sladjana
AU - Balic, Anamaria
AU - Hidalgo, Manuel
AU - Erkan, Mert
AU - Kleeff, Joerg
AU - Scarpa, Aldo
AU - Sainz, Bruno
AU - Heeschen, Christopher
N1 - Funding Information:
We thank A. González-Neira and L. Moreno from the CNIO Human Genotyping-CEGEN Unit for performing the TaqMan OpenArray SNAP analysis, and S.M. Trabulo and M. Tatari for their excellent in vivo technical assistance. The research was supported by the ERC Advanced Investigator Grant (Pa-CSC 233460), the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 256974 (EPC-TM-NET) and no. 602783 (CAM-PaC), the Associazione Italiana Ricerca Cancro (AIRC grant no. 12182 to A.S.), the Italian Cancer Genome Project Ministry of University and Research (FIRB RBAP10AHJB to A.S.), the FIMP-Italian Ministry of Health (CUP_J33G13000210001), the Subdirección General de Evaluación y Fomento de la Investigación, Fondo de Investigación Sanitaria (PS09/02129 & PI12/02643) and the Programa Nacional de Internacionalización de la I+D, Subprogramma: FCCI 2009 (PLE2009-0105; both Ministerio de Economía y Competitividad (es), Spain). M.C. was supported by the La Caixa Predoctoral Fellowship Program.
Publisher Copyright:
© 2014 Nature America, Inc.
PY - 2014/10/30
Y1 - 2014/10/30
N2 - 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.
AB - 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.
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U2 - 10.1038/nmeth.3112
DO - 10.1038/nmeth.3112
M3 - Article
C2 - 25262208
AN - SCOPUS:84908605558
SN - 1548-7091
VL - 11
SP - 1161
EP - 1169
JO - Nature Methods
JF - Nature Methods
IS - 11
ER -