C/Ebp Beta 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/EBP is thought to play an important role in CRC invasion and metastasis. In this study, we assessed whether C/EBP-mediated tumor invasion was dependent on MMP3, the expression of which is upregulated by C/EBP. We then determined whether C/EBP 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/EBP 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/EBP and MMP3 expression was determined by Pearson's correlation analysis. Results: Both mRNA and protein levels of MMP3 were upregulated by C/EBP overexpression and downregulated by C/EBP siRNA in HCT116 CRC cell cultures. C/EBP-enhanced tumor cell invasion was inhibited by MMP3 siRNA. In human CRC patients, C/EBP levels were correlated with MMP3 levels and metastatic status. Conclusions:C/EBP upregulation promoted tumor cell invasion in an MMP3-dependent manner in vitro and was associated with metastatic status in CRC.