Overexpression of cadherins suppresses pulmonary metastasis of osteosarcoma in vivo.

摘要: Osteosarcoma by nature shows aggressive pulmonary metastasis; however, the underlying molecular mechanisms remain unclear. We previously showed that N-cadherin and cadherin-11 (OB-cadherin), which are highly expressed in normal osteoblasts, anomalously human osteosarcoma (Kashima et al., Am J Pathol 1999;155:1549-55). In present study, we examined role of cadherins metastasis using mouse cell line Dunn its metastatic subline LM8. Oligonucleotide array RT-PCR analyses demonstrated LM8 cells did not express appreciable levels several members cadherin family, Western blot analysis confirmed P-cadherin, E-cadherin, or protein. therefore investigated functional consequences overexpression on migration vivo potential cells. Several clones were isolated exogenous localized to membrane able bind beta-catenin. Overexpression affect proliferation but caused an inhibitory effect vitro. N-cadherin- cadherin-11-overexpressing exhibited a marked reduction their ability form metastases, with significant decreases lung weight number lesions, as well size primary lesions at s.c.-inoculated site. These observations demonstrate disruption cadherin-11-mediated cell-cell adhesion is critical osteosarcoma.