Down-regulation of β3-integrin inhibits bone metastasis of small cell lung cancer

Bone is one of the most frequent targets of small cell lung cancer (SCLC) metastasis, but the molecular mechanism remains unclear. beta 3-integrin plays an important role in invasion of various kinds of tumors. Yet, its role in bone-metastasis of SCLC is still unknown. In this study, we first examined the expression of beta 3-integrin in SBC-5 and SBC-3 cells by real-time PCR, western blot and immunofluorescence. We found that, compared to none bone-metastatic SBC-3 cells, beta 3-integrin was highly expressed in SBC-5 cells, a specific bone-metastatic SCLC cells line characterized in our previous study. We next constructed beta 3-integrin siRNA and transfected SBC-5 cell line, and found that beta 3-integrin siRNA significantly down-regulated the beta 3-integrin mRNA level and protein expression in SBC-5 cell line. We further found that inhibition of beta 3-integrin significantly reduced tumor cell proliferation and induced apoptosis. In addition, the beta 3-integrin down-regulated cells presented significant decrease in cell adhesion, migration and invasion activity. Our results suggest the beta 3-integrin has an essential effect on tumor cell proliferation and progression, and may be a potential therapeutic target for the prevention of skeletal metastases of lung cancer.