Intracellular autofluorescence: A biomarker for epithelial cancer stem cells

Irene Miranda-Lorenzo, Jorge Dorado, Enza Lonardo, Sonia Alcala, Alicia G. Serrano, Jenifer Clausell-Tormos, Michele Cioffi, Diego Megias, Sladjana Zagorac, Anamaria Balic, Manuel Hidalgo, Mert Erkan, Joerg Kleeff, Aldo Scarpa, Bruno Sainz, Christopher Heeschen

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1161-1169
Number of pages9
JournalNature Methods
Volume11
Issue number11
DOIs
StatePublished - Oct 30 2014

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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