The gene
MT3-MMP (also known as MMP16) encodes the
membrane type 3 matrix metalloproteinase, which is a member of the
matrix metalloproteinase (
MMP) gene family. Several
MMPs are associated with migration in
colorectal cancer (CRC). However, the methylation status of the
MT3-MMP promoter in CRC has not been reported. The methylation status and expression levels of
MT3-MMP were investigated in primary
tumor tissues and adjacent normal tissues in 105 patients with CRC, one normal colon cell line (CCD18Co), and three CRC cell lines (SW480, DLD-1, and LoVo) by quantitative methylation-specific PCR and real-time PCR.
MT3-MMP was hypermethylated in 82 of 105 CRC tissues (78%), 30 of 105 adjacent normal tissues (29%), and two of 11 normal colon tissues (18%).
MT3-MMP mRNA was significantly reduced in CRC compared with that in adjacent normal tissues (P < 0.05). The methylation-mediated downregulation of
MT3-MMP was restored by treatment with
5-aza-2'-deoxycytidine in two CRC cell lines, and
MT3-MMP promoter activity was significantly reduced by methylation. The knockdown of
MT3-MMP induced cell migration, but overexpressed
MT3-MMP reduced cell migration in CRC cells. These results demonstrate that the
MT3-MMP promoter is frequently hypermethylated in CRC and that downregulation of
MT3-MMP may be important for cell migration in CRC.