ECM1 was one of the few up-regulated extracellular matrix associated proteins. This protein has previously been found to be up-regulated at the mRNA level in cholesteatoma compared with retroauricular skin. It interacts with many other extracellular matrix proteins, acts as negative regulator of bone mineralization, promotes angiogenesis, and may inhibit MMP9 action. It has also been associated with migration and invasion in cancer, and the epidermal expression is minimal under normal conditions. In the extracellular matrix network and from the topscoring proteins in Tables 3 and 4, several other differentiallyexpressed proteins in cholesteatoma showed regulations that can promote cancer-like alterations. Down-regulation of the nidogens de-stabilizes the basement membrane and has been associated with Bay 11-7085 cancer formation. Neck of cholesteatoma and cholesteatoma sack showed very low levels of these proteins. The cell adhesion protein CEACAM6 was found to be highly up-regulated in cholesteatoma compared with the tympanic membrane and EACS, in particular. Over-expression has been shown to increase tumor growth and suppress PI3/AKT-dependent apoptosis in head and neck cancer. Its mRNA levels have recently been shown to be up-regulated, as well. Profilin-2 was deficient in the three cholesteatoma replicates, but was found in high levels in all three replicates of the tympanic membrane, EACS, and mucosa. Profilin-2 is a regulator of actin polymerization, and it has recently been shown that its down-regulation enhances invasion of cells and it is associated with poor prognoses in cancer. Investigations of factors with influence on the growth of cholesteatoma, such as proliferation and apoptosis, have shown varying results. Our recent cytokine analyses revealed an up-regulation of the skin hyperplasia inducing IL21 in cholesteatoma. The decreased migration of epithelial cells combined with increased cell death indicated by the present study may contribute to the accumulation of material and expansion of the tumor.The special self-cleaning properties of the tympanic membrane and ear canal depend on Brinzolamide efficient lateral migration and controlled desquamation, and disturbances in the desquamation of the ear canal skin have previously been shown to halt migration.