Stem cell characteristics of cell sub-populations in cell lines derived from head and neck cancers of Fanconi anemia patients.
Increasing evidence indicates that cancer growth is driven by a sub-population of self-renewing cancer stem cells (CSCs) and that clinical problems of tumor recurrence after therapy may be related to differential resistance of CSCs to therapeutic elimination. Fanconi anemia (FA) is an autosomal recessive disorder associated with deficiencies of DNA repair and a greatly enhanced risk of hematopoietic malignancies and of head and neck squamous cell carcinoma (HNSCC). In FA patients, lack of DNA repair complicates therapies acting through DNA damage and alternative approaches, such as targeting signaling pathways associated with stem cell maintenance, might be of particular benefit. To assess effects of FA gene defects on the expression of stem cell properties, CSC patterns in cell lines derived from FA-related and sporadic HNSCC were compared. As for sporadic cell lines, FA cell lines showed colony morphologies associated with stem cell patterns. In all cell lines, cells with strong staining for CD44 (CD44(high) ) showed lower rates of apoptosis and a greater DNA damage induced block in the G2 phase of the cell cycle than CD44(low) cells. Mitomycin C, and UVB increased overall rates of apoptosis for both sporadic and FA cell lines, although FA cells tended to be more sensitive to apoptotic induction. Fluorescence activated cell sorting, immunohistochemistry, and QPCR indicated distinctly different patterns of gene expression of CD44(high) and CD44(low) cells in both sporadic and FA cell lines.
Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Luke
L
Gammon
Adrian
A
Biddle
Bilal
B
Fazil
Lisa
L
Harper
Ian C
IC
Mackenzie
D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D005199:Fanconi Anemia / Q000150:complications* / Q000235:genetics; D016195:G2 Phase / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000150:complications / Q000235:genetics / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000473:pathology*
D018960:Hyaluronan Receptors