S100A7 (Psoriasin) mediates anoikis resistance and tumor progression in squamous cell carcinoma of the oral cavity

Abstract

Squamous Cell Carcinoma of the Oral Cavity (SSCOC) is a leading cause of cancer deaths worldwide. Although local recurrence and metastases account for most of the deaths from this disease, information on the mechanisms of oral cancer progression and metastasis is sparse. Evasion of cell death has been shown to be an important factor for the progression of other cancers. Normal oral squamous epithelia grow adherent to a basement membrane, and, when detached from the extracellular matrix, undergo programmed cell death (anoikis). Our previous studies have shown that acquisition of anoikis-resistance is an important step in oral cavity tumor progression, and by performing cDNA microarray studies on anoikis-resistant cell lines that we had generated, we have identified several genes that are expressed in anoikis-resistant cells under detached conditions. One of these is the S100A7 protein and confirmatory studies with Western and Northing blotting demonstrate that the S100A7 protein is expressed in detached, anoikis-resistant oral cancer cells but not in detached anoikis-sensitive cells. Additional studies using immunohistochemistry and western blotting of human oral cancer tumor specimens and saliva from tumor bearing patients and normals, demonstrate that this protein is expressed in the suprabasal layer of normal oral epithelia, dysplastic epithlium, saliva, and well but not poorly-differentiated oral cancers. Furthermore, stable transfecion of S100A7 into the Tu167 anoikis sensitive cell line led to anoikis-resistance of these cells and transfection of S100 A7 siRNA in the the anoikis-resistant JMAR cell line induced anoikis. Growth of Tu167 S100A7 transfectants in a nude mouse orthotopic model of oral cancer revealed that S100A7 expression confers a more aggressive phenotype on a relatively indolent tumor forming cell line. These data have led us to hypothesize that S100A7 is important factor in mediating anoikis-resistance of oral cancer cells and local tumor progression, and that the identification of S100A7 in saliva and oral cell scrapings might be useful as a screening mechanism for early detection of primary and recurrent SCCOC tumors.