Downregulated IGFBP7 facilitates liver metastasis by modulating epithelial‑mesenchymal transition in colon cancer.

Abstract

Distant metastasis is a major cause of cancer-associated mortality in patients with colon cancer. Insulin-like growth factor binding protein 7 (IGFBP7) has been identified as a crucial inhibitor of human cancer. However, the role of IGFBP7 in the pathogenesis of metastatic colon cancer has not been investigated. In the present study, the expression of IGFBP7 in 81 pairs of colon cancer tissues and adjacent normal tissues were investigated using immunohistochemistry. Furthermore, 24 pairs of primary colon cancer and matched liver metastasis tissues were analyzed. LοVο cells with IGFBP7-knockdown and HT-29 cells with IGFBP7-overexpression were employed. The expression levels of E-cadherin, N-cadherin and Vimentin were quantified and compared. Significant alterations in the expression of IGFBP7 between late stage (III + IV) colon cancer and adjacent normal colonic mucosa were observed. (P=0.031). The association between IGFBP7 and epithelial-mesenchymal transition (EMT) markers were validated in primary colon cancer and matched liver metastasis tissues. The invasive front of liver metastatic colon tissues revealed reduced IGFBP7 expression. Additionally, knockdown of IGFBP7 in LοVο cells resulted in decreased E-cadherin, and increased N-cadherin and Vimentin expression compared with the control group. Overexpression of IGFBP7 in HT-29 cells induced an upregulation of E-cadherin; however, the N-cadherin and Vimentin levels were decreased. In conclusion, the results of the present study suggested that IGFBP7 may prevent colon cancer metastasis by inhibiting EMT, and serves as a potential diagnostic marker and therapeutic target for patients with colon cancer.