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.