TY - JOUR
T1 - Paracrine loops of keratinocyte stimulation in cholesteatoma tissue
T2 - An immunofluorescence, transmission electron microscopy, and molecular study
AU - D'Alessandro, Federica
AU - Raffa, Salvatore
AU - Murè, Carmelo
AU - Kovacs, Daniela
AU - Torrisi, Maria Rosaria
AU - Barbara, Maurizio
PY - 2010/9
Y1 - 2010/9
N2 - Hypothesis: In relation to the keratinocyte growth factor (KGF) expression in cholesteatoma tissue, the inflammatory infiltrate present in this disease could play a relevant role in the paracrine stimulation of keratinocytes. Background: Cholesteatoma is a temporal bone pathologic disease characterized by active proliferation of epithelial cells, with progressive growth and involvement of the neighboring middle/inner ear structures. The pathogenetic mechanism underlying the hyperproliferation of keratinocytes is not yet fully clarified. It has been suggested that keratinocyte proliferation and migration could be mediated by several autocrine and paracrine growth factors and their receptors. A previous study has reported that the expression of KGF receptor is increased in more differentiated areas of the cholesteatoma tissue, whereas the expression of the epidermal growth factor receptor is associated with proliferative and migratory areas of the lesion. Methods: Fresh cholesteatoma samples were collected during surgical procedures. Serial cryosections were examined by conventional hematoxylin and eosin or by immunofluorescence with antipancytokeratin antibodies. The ultrastructural features were analyzed by transmission electron microscopy. The expression of KGF, K1, and filaggrin in the samples was evaluated by quantitative reverse transcription-polymerase chain reaction and correlated with the dermal degree of inflammatory infiltrate and the presence of stromal cells. Results: Increased expression of KGF was associated with strong levels of the inflammatory infiltrate. Conclusion: These results would suggest that KGF up-modulation is a consequence of fibroblast stimulation by inflammatory cells and that this paracrine loop could be responsible not only for the hyperproliferation of keratinocytes in cholesteatoma tissue but also for the deregulation of epidermal differentiation.
AB - Hypothesis: In relation to the keratinocyte growth factor (KGF) expression in cholesteatoma tissue, the inflammatory infiltrate present in this disease could play a relevant role in the paracrine stimulation of keratinocytes. Background: Cholesteatoma is a temporal bone pathologic disease characterized by active proliferation of epithelial cells, with progressive growth and involvement of the neighboring middle/inner ear structures. The pathogenetic mechanism underlying the hyperproliferation of keratinocytes is not yet fully clarified. It has been suggested that keratinocyte proliferation and migration could be mediated by several autocrine and paracrine growth factors and their receptors. A previous study has reported that the expression of KGF receptor is increased in more differentiated areas of the cholesteatoma tissue, whereas the expression of the epidermal growth factor receptor is associated with proliferative and migratory areas of the lesion. Methods: Fresh cholesteatoma samples were collected during surgical procedures. Serial cryosections were examined by conventional hematoxylin and eosin or by immunofluorescence with antipancytokeratin antibodies. The ultrastructural features were analyzed by transmission electron microscopy. The expression of KGF, K1, and filaggrin in the samples was evaluated by quantitative reverse transcription-polymerase chain reaction and correlated with the dermal degree of inflammatory infiltrate and the presence of stromal cells. Results: Increased expression of KGF was associated with strong levels of the inflammatory infiltrate. Conclusion: These results would suggest that KGF up-modulation is a consequence of fibroblast stimulation by inflammatory cells and that this paracrine loop could be responsible not only for the hyperproliferation of keratinocytes in cholesteatoma tissue but also for the deregulation of epidermal differentiation.
KW - Cholesteatoma
KW - Immunofluorescence
KW - Keratinocyte growth factor
KW - Real-time polymerase chain Reaction
KW - Transmission electron microscopy
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U2 - 10.1097/MAO.0b013e3181ec1bb9
DO - 10.1097/MAO.0b013e3181ec1bb9
M3 - Article
C2 - 20679958
AN - SCOPUS:77956341404
VL - 31
SP - 1163
EP - 1169
JO - Otology and Neurotology
JF - Otology and Neurotology
SN - 1531-7129
IS - 7
ER -