3732

CD82

4F9|C33|GR15|IA4|KAI1|R2|SAR2|ST6|TSPAN27;CD82 molecule;CD82;CD82 molecule

C33 antigen|CD82 antigen|inducible membrane protein R2|kangai 1 (suppression of tumorigenicity 6, prostate; CD82 antigen (R2 leukocyte antigen, antigen detected by monoclonal and antibody IA4))|metastasis suppressor Kangai-1|tetraspanin-27|tspan-27

11p11.2

protein-coding

Count: 3; Pubmed_search,TAG,Generif

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.

The KAI1 gene is identified as a tumor metastasis suppressor gene in many types of cancer. We examined KAI1 gene and its protein KAI1/CD82 expression by in situ hybridization and immunohistochemical analysis, and found that KAI1 mRNA and protein expression were inversely correlated with lymph node and distant metastasis in digestive tract carcinomas, but not with age and gender of the patient, or with tumor differentiation. Moreover, KAI1/CD82 protein expression positively reflected the survival outcome of patients. Western blot analysis showed that VP-16 increased KAI1/CD82 protein expression obviously in various cancer cell lines, especially in those that were highly metastatic. This increased KAI1/CD82 expression was associated with its translocation from the cytomembrane to the nucleus, in which it interacted with nuclear p53 protein, forming a strong complex, observed by confocal microscopy and co-immunoprecipitation, respectively. In nude mice, after feeding with VP-16, the number of tumors metastasized from spleen to liver was obviously reduced, and KAI1/CD82 protein expression became stronger in those metastatic tumors. Accordingly, this demonstrated that KAI1 might be used as an indicator for predicting the clinical outcome, and VP-16 may be clinically considered as a promising candidate for anti-metastasis with regard to its potential to upregulate KAI1 expression.