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Osteoactivin regulates head and neck squamous cell carcinoma invasion by modulating matrix metalloproteases
Author(s) -
Arosarena Oneida A.,
Barr Eric W.,
Thorpe Ryan,
Yankey Hilary,
Tarr Joseph T.,
Safadi Fayez F.
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25900
Subject(s) - gelatinase , gene silencing , matrix metalloproteinase , head and neck squamous cell carcinoma , cancer research , downregulation and upregulation , extracellular matrix , cell culture , chemistry , metalloproteinase , cell , gelatinase a , cancer cell , metastasis , cell migration , biology , cancer , medicine , head and neck cancer , gene , biochemistry , genetics
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.