Distinct P-cadherin expression in cultured normal human keratinocytes and squamous cell carcinoma cell lines.
Spatially regulated expression of E (epithelial)- and P (placental)-cadherins is crucial for maintaining normal epidermal architecture. In cutaneous squamous cell carcinomas (SCCs), aberrant P-cadherin expression is often observed in "squamoid" cancer cells, whereas E-cadherin expression in cancer cells is generally reduced. Therefore, it is plausible that SCC cells have acquired the ability to express P-cadherin and that P-cadherin plays a role in tumor progression. To address the issue, the in vitro effect of extracellular calcium on differentiation is a good model for investigating P-cadherin in normal and neoplastic skin. With elevations in extracellular calcium, human SCC cell line (DJM-1) cells initiate de novo synthesis of P-cadherin and express P-cadherin on the cell surface, whereas in normal human keratinocytes, P-cadherin expression on the cell surface is enhanced via the translocation from the cytosol to the cell membrane and/or the stabilization of P-cadherin at the cell surface. DJM-1 cells maintain P-cadherin expression on the cell surface at high levels for over 4 days after calcium elevation, whereas normal human keratinocytes cannot sustain cell surface P-cadherin when the cells are cultured in high calcium for more than 2 days. P-cadherin synthesis in DJM-1 cells is regulated at translational levels by extracellular calcium concentrations. SCC cells have the ability to produce P-cadherin by a mechanism not observed in normal keratinocytes, which might relate to the aberrant expression of P-cadherin in SCC of the skin.
Wakita
H
H
Department of Dermatology, Hamamatsu University School of Medicine, Japan. wakita@hama-med.ac.jp
Shirahama
S
S
Furukawa
F
F
D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D018613:Microscopy, Confocal; D014176:Protein Biosynthesis; D014407:Tumor Cells, Cultured
D015820:Cadherins; D002118:Calcium