Role of IGFBP-2 in oral cancer metastasis

Cancer metastasis is one of most main causes of failure in cancer treatment. Nonetheless, more than half of oral cancer patients were diagnosed as advanced oral cancer with dramatically decreased 5-year survival rate to lower than 20%, while the stages become more advanced. In order to improve oral cancer treatment, the identification of cancer metastatic biomarkers and mechanisms is critical. In the current study, two pairs of oral squamous cell carcinoma lines, OC3/C9, and invasive OC3-I5/C9-I5were used as model systems to investigate invasive mechanism as well as to identify potential therapy-associated targets. Based on our previous proteomic analysis, insulin-like growth factor-binding protein 2 (IGFBP-2) was reported participating in oral cancer metastasis. Subsequent studies have applied interference RNA as well as recombinant protein techniques to confirm the roles of IGFBP-2 in oral cancer metastasis and examine their potency in regulating invasion as well as the mechanism IGFBP-2 involved. The results demonstrated that expression of epithelial-mesenchymal transition (EMT) markers including Twist, Snail1, SIP1, profilin, vimentin, uPA and MMP9 were increased in both OC3-I5 and C9-I5 compared to OC3 and C9 cells, while E-cadherin expression was down-regulated in the OC3-I5 and C9-I5 cells. Moreover, IGFBP-2 is shown to affect not only migration and invasion but also wound healing ability and cell proliferation. Our results also revealed that uPA is a downstream target of IGFBP-2 to intermediate oral cancer metastasis. To sum up, the current studies indicated that elevated IGFBP-2 is strongly correlated with oral cancer metastasis and progression, and that it could potentially serve as a prognostic biomarker as well as an innovative target for the treatment of oral cancer invasion.