cancer stem cell; head and neck cancer; epithelial mesenchymal transition
610 Medizin und Gesundheit
Accumulating evidence suggests that self-renewal and differentiation capabilities reside only in a subpopulation of tumor cells, termed cancer stem cells (CSCs) that can be identified by their aldehyde-dehydrogenase-isoform-1 (ALDH1) activity. We quantified and enriched ALDH1+ cells within HNSCC cell lines by an anchorage independent culture method and subsequently characterized their phenotypic and functional properties and epithelial-to-mesenchymal transition (EMT). On patients’ tumor samples, we investigated the relationship of ALDH1 andα-smooth muscle actin (SMA) expression to metastasis of HNSCC. All cell lines formed spheroids that could self-renew and be serially re-passaged. ALDH1 expression was significantly higher in spheroid-derived cells (SDCs). ALDH1+ cells possessed self-renewal capability. SDCs had significantly higher invading activity. mRNA of the stemness-related transcription factor (TF) genes Sox2, Nanog, and Oct3/4 was significantly increased in SDCs of all cell lines. SDCs had a higher G0 phase proportion, showed high-level expression of α-SMA and Vimentin, but significantly decreased E-Cadherin expression. In 60 tumor samples from HNSCC patients, ALDH1 andα-SMA expression level was proven to closely correlate to lymph node metastasis. HNSCC-lines harbor potential CSCs, characterized by ALDH1 and stemness marker TF expression as well as properties like invasiveness, quiescence, and EMT. CSCs can be enriched by anchorage-independent culture techniques, which may be important for the investigation of their contribution to therapy resistance, tumor recurrence and metastasis.
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