C/EBPβ Promotion of MMP3-Dependent Tumor Cell Invasion and Association with Metastasis in Colorectal Cancer.

Aims: Tumor metastasis is a significant obstacle to curing colorectal cancer (CRC). C/EBPβ is thought to play an important role in CRC invasion and metastasis. In this study, we assessed whether C/EBPβ-mediated tumor invasion was dependent on MMP3, the expression of which is upregulated by C/EBPβ. We then determined whether C/EBPβ upregulation was associated with MMP3 levels and metastatic status in human CRC patients.

Materials And Methods: A total of 102 patients were recruited for this study. mRNA and protein levels of C/EBPβ and MMP3 in CRC cell lines and patient specimens were determined by reverse transcription-polymerase chain reaction and western blot, respectively. Tumor cell invasion was analyzed using an in vitro Matrigel Invasion Assay. The correlation between C/EBPβ and MMP3 expression was determined by Pearson's correlation analysis.

Results: Both mRNA and protein levels of MMP3 were upregulated by C/EBPβ overexpression and downregulated by C/EBPβ siRNA in HCT116 CRC cell cultures. C/EBPβ-enhanced tumor cell invasion was inhibited by MMP3 siRNA. In human CRC patients, C/EBPβ levels were correlated with MMP3 levels and metastatic status.

Conclusions: C/EBPβ upregulation promoted tumor cell invasion in an MMP3-dependent manner in vitro and was associated with metastatic status in CRC.