title: Secretory leukocyte protease inhibitor (SLPI) expression and tumor invasion in oral squamous cell carcinoma.
abstract: Differential expression of secretory leukocyte protease inhibitor (SLPI) impacts on tumor progression. SLPI directly inhibits elastase and other serine proteases, and regulates matrix metalloproteinases, plasminogen activation, and plasmin downstream targets to influence invasion. We examined tissues from human oral squamous cell carcinoma (OSCC) for SLPI expression in parallel with proteases associated with tumor progression and evaluated their relationships using tumor cell lines. Significantly decreased SLPI was detected in OSCC compared to normal oral epithelium. Furthermore, an inverse correlation between SLPI and histological parameters associated with tumor progression, including stage of invasion, pattern of invasion, invasive cell grade, and composite histological tumor score was evident. Conversely, elevated plasmin and elastase were positively correlated with histological parameters of tumor invasion. In addition to its known inhibition of elastase, we identify SLPI as a novel inhibitor of plasminogen activation through its interaction with annexin A2 with concomitant reduced plasmin generation by macrophages and OSCC cell lines. In an in vitro assay measuring invasive activity, SLPI blocked protease-dependent tumor cell migration. Our data suggest that SLPI may possess antitumorigenic activity by virtue of its ability to interfere with multiple requisite proteolytic steps underlying tumor cell invasion and may provide insight into potential stratification of oral cancer according to risk of occult metastasis, guiding treatment strategies.
authors.affiliation: Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Wen
authors.forename: Nikolaos G
authors.initials: NG
authors.lastname: Nikitakis
authors.forename: Risa
authors.initials: R
authors.lastname: Chaisuparat
authors.forename: Teresa
authors.initials: T
authors.lastname: Greenwell-Wild
authors.forename: Maria
authors.initials: M
authors.lastname: Gliozzi
authors.forename: Wenwen
authors.initials: W
authors.lastname: Jin
authors.forename: Azita
authors.initials: A
authors.lastname: Adli
authors.forename: Niki
authors.initials: N
authors.lastname: Moutsopoulos
authors.forename: Tanxia
authors.initials: T
authors.lastname: Wu
authors.forename: Gary
authors.initials: G
authors.lastname: Warburton
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Wahl
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017306:Annexin A2 / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005341:Fibrinolysin / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D010196:Pancreatic Elastase / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D017306:Annexin A2; D061965:Matrix Metalloproteinase Inhibitors; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D010958:Plasminogen; D010196:Pancreatic Elastase; D005341:Fibrinolysin; D020782:Matrix Metalloproteinases