Overexpression of FMNL2 is closely related to metastasis of colorectal cancer

Abstract

Background and aims: Formin-like 2 (FMNL2) is a member of diaphanous-related formins which can control the actin-dependent processes such as cell motility and invasion. In this study, we investigated the expression of FMNL2 in colorectal cancer (CRC) and its correlation with CRC metastasis. Patients-methods: Paraffin-embedded specimens of CRC (including 75 primary CRC tumors and 45 corresponding metastatic lymph nodes) and normal colorectal mucosa (30 samples) were immunostained with a FMNL2 antibody. Thirty-two paired snap-frozen tumor tissues and adjacent normal colorectal mucosa were subjected to real-time reverse-transcription polymerase chain reaction (RT-PCR). Six CRC cell lines (SW480, SW620, SW480/M5, LoVo, LS174T, and HT29) were assayed for FMNL2 expression by Western blotting and real-time RT-PCR. Their invasive abilities in vitro were determined by Boyden chamber assay. Results: The immunohistochemical analysis showed FMNL2 expression was considerably higher in CRC tumors and corresponding metastatic lymph nodes than in normal colorectal mucosa (P<0.05, respectively). Elevated FMNL2 expression was significantly correlated with lymphatic metastasis of CRC (P<0.05). Real-time RT-PCR analysis confirmed the results obtained by immunohistochemistry. At mRNA and protein levels, FMNL2 expression was substantially upregulated in cell lines derived from CRC metastases (SW620, SW480/M5, and LoVo) compared to ones derived from primary CRC (HT29, LS174T, and SW480; P<0.05). In vitro cell invasive assay demonstrated that the former three cell lines had higher invasive ability than the latter cell lines. Conclusions: FMNL2 may play an important role in the metastasis of CRC and may be a useful marker for metastasis of CRC. © Springer-Verlag 2008.