title: Secretory leukocyte protease inhibitor is associated with MMP-2 and MMP-9 to promote migration and invasion in SNU638 gastric cancer cells.
abstract: Secretory leukocyte protease inhibitor (SLPI) protects tissue from proteases, and promotes cell proliferation and healing during inflammatory response. SLPI is also overexpressed in gastric, lung and ovarian cancers, which accelerates the metastasis of cancer cells. Matrix metalloproteinases-2, -9 (MMP-2 and MMP-9) are overexpressed in high metastatic cancers, and promote the migration of cancer cells through collagen degradation. SLPI and MMP-2, -9 are critical factors in stimulating the metastatic processes but there are no reports of a direct correlation between these molecules. Therefore, this study examined the role of SLPI related to MMP-2 and MMP-9 using two gastric cancer cell lines, such as characterized non-metastatic SNU484 and highly metastatic SNU638 cells. SLPI, MMP-2 and MMP-9 mRNA and protein expression were higher in SNU638 cells than in SNU484 cells. In addition, the rate of cell migration and invasion was higher in the SNU638 cells than in SNU484 cells. Interestingly, after treatment with SLPI, the rate of migration and invasion was higher in the SNU484 cells than in the positive control (PC) SNU484 cells. The rate of migration was also higher in the SNU638 cells after SLPI treatment than in the SNU638 cells (PC) but the invasion rate was not changed. The expression and secretion of MMP-2 and MMP-9 as well the rate of cell migration and invasion were significantly lower in SLPI-siRNA transfected SNU638 cells (si-SLPI/SNU638) but higher in SLPI-treated SNU484 cells (SNU484 + SLPI). Strong Elk-1 phosphorylation was detected in SNU484 + SLPI and SNU638 cells but was barely detectable in SNU484 and si-SLPI/SNU638 cells. These results show that SLPI promotes the metastasis of SNU638 gastric cancer cells by increasing MMP-2 and MMP-9 expression through Elk-1 signaling, indicating its role as a signaling molecule not a protease inhibitor.
authors.affiliation: Department of Oral Histology and Developmental Biology, Chosun University, Gwangju 501‑759, Republic of Korea.
authors.forename: Baik-Dong
authors.initials: BD
authors.lastname: Choi
authors.forename: Soon-Jeong
authors.initials: SJ
authors.lastname: Jeong
authors.forename: Guanlin
authors.initials: G
authors.lastname: Wang
authors.forename: Jin-Ju
authors.initials: JJ
authors.lastname: Park
authors.forename: Do-Seon
authors.initials: DS
authors.lastname: Lim
authors.forename: Byung-Hoon
authors.initials: BH
authors.lastname: Kim
authors.forename: Yong-Ick
authors.initials: YI
authors.lastname: Cho
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Kim
authors.forename: Moon-Jin
authors.initials: MJ
authors.lastname: Jeong
mesh_terms: D015152:Blotting, Northern; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9