Aberrant expression and altered cellular localization of desmosomal and hemidesmosomal proteins are associated with aggressive clinicopathological features of oral squamous cell carcinoma.
Disruption of cell adhesion plays a central role in dedifferentiation, invasion, and metastasis of various cancers. The desmosome and hemidesmosome are anchoring junctions that control cell-cell and cell-matrix adhesion, respectively. To clarify their contributions in mediating the biological properties of oral cancer, we immunohistochemically examined the expression of desmoglein 1 (DSG1), DSG2, DSG3, desmocollin 2 (DSC2), integrin beta 4 (ITGB4), laminin gamma chain 2 (LAMC2), and collagen type 17 alpha 1 (COL17A1) in 51 cases of oral squamous cell carcinoma. On normal oral epithelial cells, DSG1, DSG3, DSC2, and COL17A1 were expressed on the plasma membrane, while ITGB4 and mature LAMC2 were present at the basement membrane. In cancer, the expression of DSG1, DSG3, DSC2, and COL17A1 decreased and internalized to the cytoplasm. Cytoplasmic expression of DSG2, ITGB4, and LAMC2 was induced in the cancer cells facing to the stroma. We scored immunohistochemical expression and correlated this to clinicopathological parameters including histologic differentiation, pattern of invasion, and presence of lymph node metastasis. Decrease of DSG3 and DSC2 expression correlated with a more aggressive cancer phenotype: less differentiated and more invasive histologic features and a higher incidence of nodal metastasis. Lower COL17A1 and higher LAMC2 expression were also associated with a more aggressive phenotype. The present study demonstrates that aberrant expression and altered cellular localization of desmosomal and hemidesmosomal proteins are associated with aggressive clinicopathological features of oral cancer. This reinforces the notion that disturbance of the keratin-associated anchoring junctions confers aggressive features to cancer cells.
Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo, 113-0034, Japan.
Zhao
Z
Xin
Akira
A
Yamaguchi
Kei
K
Sakamoto
D015820:Cadherins / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002454:Cell Differentiation; D051180:Desmoplakins / Q000378:metabolism; D003896:Desmosomes / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*
D015820:Cadherins; D051180:Desmoplakins