MMP28 (epilysin) as a novel promoter of invasion and metastasis in gastric cancer
1 Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China
2 Hillman Cancer Center Lab, Department of Pathology, Pittsburgh University, G21 5117 Center Ave. Pittsburgh, PA 15206, USA
3 Department of Cell and Molecular Biology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
4 Translational Research Center, Second Hospital, The Second Clinical School, Nanjing Medical University, Nanjing, China
BMC Cancer 2011, 11:200 doi:10.1186/1471-2407-11-200Published: 26 May 2011
The purpose of this study was to investigate invasion and metastasis related genes in gastric cancer.
The transwell migration assay was used to select a highly invasive sub-line from minimally invasive parent gastric cancer cells, and gene expression was compared using a microarray. MMP28 upregulation was confirmed using qRT-PCR. MMP28 immunohistochemistry was performed in normal and gastric cancer specimens. Invasiveness and tumor formation of stable cells overexpressing MMP28 were tested in vitro and in vivo.
MMP28 was overexpressed in the highly invasive sub-cell line. Immunohistochemistry revealed MMP28 expression was markedly increased in gastric carcinoma relative to normal epithelia, and was significantly associated with depth of tumor invasion, lymph node metastasis and poorer overall survival. Ectopic expression of MMP28 indicated MMP28 promoted tumor cell invasion in vitro and increased gastric carcinoma metastasis in vivo.
This study indicates MMP28 is frequently overexpressed during progression of gastric carcinoma, and contributes to tumor cell invasion and metastasis. MMP28 may be a novel therapeutic target for prevention and treatment of metastases in gastric cancer.