Plasminogen activator/plasmin system suppresses cell-cell adhesion of oral squamous cell carcinoma cells via proteolysis of E-cadherin.
The participation of plasminogen activator/plasmin system in the expression and function of E-cadherin was examined in oral squamous cell carcinoma (SCC) cells. Treatment of SCC cells with plasminogen reduced the Ca2+-dependent cell aggregation. SCC cells expressed E-cadherin at the cell membrane, and released a small amount of soluble E-cadherin at 80 kDa in the culture medium. Addition of plasminogen to SCC cells led to a decrease in the amount of E-cadherin of the cell membrane and the enhancement of the shedding of E-cadherin ectodomain. Plasmin directly cleaved E-cadherin of SCC cells and enhanced the motility of SCC cells. These results suggested that plasminogen activator/plasmin system might directly mediate the proteolytic processing of E-cadherin in oral SCC cells and that might facilitate the progression of oral SCC by downregulation of E-cadherin-mediated cell-cell adhesion.
Hayashido
Yasutaka
Y
Department of Molecular Oral Medicine and Maxillofacial Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima 734-8553, Japan. hayashiy@hiroshima-u.ac.jp
Hamana
Tomoaki
T
Yoshioka
Yukio
Y
Kitano
Hisataka
H
Koizumi
Koh-Ichi
K
Okamoto
Tetsuji
T
D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005341:Fibrinolysin / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D010958:Plasminogen / Q000494:pharmacology; D010960:Plasminogen Activators / Q000502:physiology*; D013997:Time Factors
D015820:Cadherins; D010958:Plasminogen; D010960:Plasminogen Activators; D005341:Fibrinolysin; D002118:Calcium