Tumor suppressor KAI1 affects integrin alphavbeta3-mediated ovarian cancer cell adhesion, motility, and proliferation.
The tetraspanin KAI1 had been described as a metastasis suppressor in many different cancer types, a function for which associations of KAI1 with adhesion and signaling receptors of the integrin superfamily likely play a role. In ovarian cancer, integrin alphavbeta3 correlates with tumor progression and its elevation in vitro provoked enhanced cell adhesion accompanied by significant increases in cell motility and proliferation in the presence of its major ligand vitronectin. In the present study, we characterized integrin alphavbeta3-mediated tumor biological effects as a function of cellular KAI1 restoration and proved for the first time that KAI1, besides its already known physical crosstalk with beta1-integrins, also colocalizes with integrin alphavbeta3. Functionally, elevated KAI1 levels drastically increased integrin alphavbeta3/vitronectin-dependent ovarian cancer cell adhesion. Since an intermediate level of cell adhesive strength is required for optimal cell migration, we next studied ovarian cancer cell motility as a function of KAI1 restoration. By time lapse video microscopy, we found impaired integrin alphavbeta3/vitronectin-mediated cell migration most probably due to strongly enhanced cellular immobilization onto the adhesion-supporting matrix. Moreover, KAI1 reexpression significantly diminished cell proliferation. These data strongly indicate that KAI1 may suppress ovarian cancer progression by inhibiting integrin alphavbeta3/vitronectin-provoked tumor cell motility and proliferation as important hallmarks of the oncogenic process.
Department of Gynecology and Obstetrics, Clinical Research Unit, Technische Universität München, Munich, Germany.
Zlatna
Z
Ruseva
Pamina Xenia Charlotte
PX
Geiger
Peter
P
Hutzler
Matthias
M
Kotzsch
Birgit
B
Luber
Manfred
M
Schmitt
Eva
E
Gross
Ute
U
Reuning
D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D051861:Kangai-1 Protein / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D021381:Protein Transport; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D019096:Vitronectin / Q000378:metabolism
C497688:CD82 protein, human; D039302:Integrin alphaVbeta3; D051861:Kangai-1 Protein; D025521:Tumor Suppressor Proteins; D019096:Vitronectin