Expression of Tiam1 and VEGF-C correlates with lymphangiogenesis in human colorectal carcinoma.

Objective: To investigate the relationship between Tiam1 and lymphangiogenesis in human colorectal carcinoma (CRC) tissues, as well as the expression of VEGF-C in a CRC cell line (HCT116) after knockdown of the Tiam1 gene with RNA interference (RNAi).

Results: In the specimens of CRC tissue, the positivity rate of Tiam1 and VEGF-C was 84% and 58%, respectively. The positivity rate of VEGF-C in the Tiam1 positive group (64.3%) was significantly higher than that in the Tiam1 negative group (25.0%). The LMVD in the Tiam1 positive group (11.35 +/- 3.34) was significantly higher than that in the Tiam1 negative group (7.38 +/- 2.27). In addition, the expression of the Tiam1 gene was efficiently blocked by RNAi. Downregulation of Tiam1 gene expression significantly suppressed HCT116 cell growth in vitro. Compared with untransfected HCT116 cells, HCT116 cells transfected with pGenesil-1-Tiam1 plasmids showed a significant decrease in the expression of VEGF-C.

Methods: The expressions of Tiam1, Rac1, VEGF-C and Podoplanin in 50 samples of CRC were detected by immunohistochemical analysis. The lymph microvessel density (LMVD) in Podoplanin positive specimens was evaluated. The results were analyzed statistically to investigate the correlation of Tiam1, VEGF-C, lymph node metastasis and other clinicopathological parameters. An shRNA eukaryotic expression vector against Tiam1 gene was constructed and transfected into HCT116 cells. The expression of Tiam1 gene was assessed by RT-PCR and western blot analysis.

Conclusions: We suggest that the Tiam1 gene may act as a crucial therapeutic target for Lymphangiogenesis in CRC.