title: Osteoactivin regulates head and neck squamous cell carcinoma invasion by modulating matrix metalloproteases.
abstract: Nearly 60% of patients with head and neck squamous cell carcinoma (HNSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell migration and invasion, which are in part dependent on extracellular matrix degradation by matrix metalloproteinases. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies, and has been shown to upregulate matrix metalloproteinase (MMP) expression and activity. To determine how OA modulates MMP expression and activity in HNSCC, and to investigate OA effects on cell invasion, we assessed effects of OA treatment on MMP mRNA and protein expression, as well as gelatinase and caseinolytic activity in HNSCC cell lines. We assessed the effects of OA gene silencing on MMP expression, gelatinase and caseinolytic activity, and cell invasion. OA treatment had differential effects on MMP mRNA expression. OA treatment upregulated MMP-10 expression in UMSCC14a (p = 0.0431) and SCC15 (p < 0.0001) cells, but decreased MMP-9 expression in UMSCC14a cells (p = 0.0002). OA gene silencing decreased MMP-10 expression in UMSCC12 cells (p = 0.0001), and MMP-3 (p = 0.0005) and -9 (p = 0.0036) expression in SCC25 cells. In SCC15 and SCC25 cells, OA treatment increased MMP-2 (p = 0.0408) and MMP-9 gelatinase activity (p < 0.0001), respectively. OA depletion decreased MMP-2 (p = 0.0023) and -9 (p < 0.0001) activity in SCC25 cells. OA treatment increased 70 kDa caseinolytic activity in UMSCC12 cells consistent with tissue type plasminogen activator (p = 0.0078). OA depletion decreased invasive capacity of UMSCC12 cells (p < 0.0001). OA's effects on MMP expression in HNSCC are variable, and may promote cancer cell invasion.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.|Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.
authors.forename: Oneida A
authors.identifier: http://orcid.org/0000-0002-2764-0820
authors.initials: OA
authors.lastname: Arosarena
authors.affiliation: Department of Physiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Barr
authors.affiliation: Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.
authors.forename: Ryan
authors.initials: R
authors.lastname: Thorpe
authors.affiliation: Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.
authors.forename: Hilary
authors.initials: H
authors.lastname: Yankey
authors.affiliation: Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Tarr
authors.affiliation: Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, Ohio.
authors.forename: Fayez F
authors.initials: FF
authors.lastname: Safadi
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D014162:Transfection
chemical_list: C503042:GPNMB protein, human; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D053505:Matrix Metalloproteinases, Secreted
keywords: cell lines; extracellular matrix; human; matrix metalloproteinases; neoplasm invasion