Loss of invasiveness in squamous cell carcinoma cells overexpressing desmosomal cadherins.
The molecular and structural characteristics of intercellular adhesion were investigated in a squamous cell carcinoma (SCCA) cell line, originally derived from an oral tumor with an invasive growth pattern. The expression of adherens junction and desmosomal components were compared with that of cultured normal oral keratinocytes. Lack of membrane association in interdesmosomal areas, the disorganization of the actin cytoskeleton and the faster cell disassembly upon E-cadherin antibody binding in SCCA cells indicated decreased functional adherens junctions. These observations were supported by a significant reduction in E-, N-, and P-cadherin protein expression. In contrast, the level of desmosomal cadherin proteins, desmoglein 1/2 and desmocollin 2, were substantially upregulated and accompanied, ultrastructurally, by increased number and size of desmosomes. Since tumor invasion suppressor capacity has been proposed for desmosomal cadherins, we investigated the in vivo invasion potential of these SCCA cells by introducing them into SCID mice. Tumors developed, but with a benign phenotype. Based on these results, we hypothesize that the benign behavior of this SCCA cell line is a consequence of overexpressed desmosomal cadherins. This SCCA cell line, therefore, represents an excellent model system to further investigate the regulation and tumor invasion suppressor potential of desmosomal adhesion molecules.
De Bruin
A
A
Institute of Animal Pathology, University of Berne, Switzerland.
Müller
E
E
Wurm
S
S
Caldelari
R
R
Wyder
M
M
Wheelock
M J
MJ
Suter
M M
MM
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D015152:Blotting, Northern; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D002448:Cell Adhesion; D003599:Cytoskeleton / Q000378:metabolism; D003896:Desmosomes / Q000378:metabolism*; D004285:Dogs; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D016513:Mice, SCID; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000943:Antigens, Differentiation; D015820:Cadherins