Overexpression of Hsp27 in a human melanoma cell line: regulation of E-cadherin, MUC18/MCAM, and plasminogen activator (PA) system.
Hsp27 is considered a potential marker for cell differentiation in diverse tissues. Several aspects linked to the differentiation process and to the transition from high to low metastatic potential were analyzed in melanoma cells transfected with Hsp27. E-cadherin plays a central role in cell differentiation, migration, and normal development. Loss of expression or function of E-cadherin has been documented in a variety of human malignancies. We observed by fluorescence-activated cell sorter (FACS) as well as immunofluorescence (IF) analysis a pronounced expression of E-cadherin in Hsp27-transfected A375 melanoma cells compared with control melanoma cells. The expression of the adhesion molecule MUC18/MCAM correlates directly with the metastatic potential of melanoma cells. In contrast to wild-type and neotransfected melanoma cells, in Hsp27-transfected cells the expression of MUC18/MCAM could not be detected by FACS and IF analysis. The plasminogen activator (PA) system plays a central role in mediating extracellular proteolysis and also in nonproteolytic events such as cell adhesion, migration, and transmembrane signaling. Hsp27 transfectants revealed elevated messenger ribonucleic acid expression of the urokinase-type PA (uPA) and its inhibitor, PA inhibitor type 1, which might indicate a neutralization effect of the proteolytic activity of uPA. Control cells failed to express both these molecules. The influence of Hsp27 expression on uPA activity and the involvement of E-cadherin could be demonstrated by use of anti-E-cadherin-blocking antibody. Our data provide evidence for an inhibitory-regulatory role of Hsp27 in tumor progression as found in our system.
Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
Silke
S
Aldrian
Ingela
I
Kindas-Mügge
Franz
F
Trautinger
Ilse
I
Fröhlich
Andrea
A
Gsur
Irene
I
Herbacek
Walter
W
Berger
Michael
M
Micksche
D015703:Antigens, CD; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis; D051929:CD146 Antigen; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D019006:Neural Cell Adhesion Molecules; D010960:Plasminogen Activators / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D051929:CD146 Antigen; D015820:Cadherins; D006360:Heat-Shock Proteins; C497902:MCAM protein, human; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D012313:RNA; D010960:Plasminogen Activators