PLoS ONE (Jan 2011)

MMP-10/stromelysin-2 promotes invasion of head and neck cancer.

  • Elsayed Mohamed Deraz,
  • Yasusei Kudo,
  • Maki Yoshida,
  • Mariko Obayashi,
  • Takaaki Tsunematsu,
  • Hirotaka Tani,
  • Samadarani B S M Siriwardena,
  • Mohammad Reza Keikhaee,
  • Guangying Qi,
  • Shinji Iizuka,
  • Ikuko Ogawa,
  • Giuseppina Campisi,
  • Lorenzo Lo Muzio,
  • Yoshimitsu Abiko,
  • Akira Kikuchi,
  • Takashi Takata

DOI
https://doi.org/10.1371/journal.pone.0025438
Journal volume & issue
Vol. 6, no. 10
p. e25438

Abstract

Read online

BackgroundPeriostin, IFN-induced transmembrane protein 1 (IFITM1) and Wingless-type MMTV integration site family, member 5B (Wnt-5b) were previously identified as the invasion promoted genes of head and neck squamous cell carcinoma (HNSCC) by comparing the gene expression profiles between parent and a highly invasive clone. We have previously reported that Periostin and IFITM1 promoted the invasion of HNSCC cells. Here we demonstrated that Wnt-5b overexpression promoted the invasion of HNSCC cells. Moreover, stromelysin-2 (matrix metalloproteinase-10; MMP-10) was identified as a common up-regulated gene among Periostin, IFITM1 and Wnt-5b overexpressing HNSCC cells by using microarray data sets. In this study, we investigated the roles of MMP-10 in the invasion of HNSCC.Methods and findingsWe examined the expression of MMP-10 in HNSCC cases by immunohistochemistry. High expression of MMP-10 was frequently observed and was significantly correlated with the invasiveness and metastasis in HNSCC cases. Next, we examined the roles of MMP-10 in the invasion of HNSCC cells in vitro. Ectopic overexpression of MMP-10 promoted the invasion of HNSCC cells, and knockdown of MMP-10 suppressed the invasion of HNSCC cells. Moreover, MMP-10 knockdown suppressed Periostin and Wnt-5b-promoted invasion. Interestingly, MMP-10 overexpression induced the decreased p38 activity and MMP-10 knockdown induced the increased p38 activity. In addition, treatment with a p38 inhibitor SB203580 in HNSCC cells inhibited the invasion.ConclusionsThese results suggest that MMP-10 plays an important role in the invasion and metastasis of HNSCC, and that invasion driven by MMP-10 is partially associated with p38 MAPK inhibition. We suggest that MMP-10 can be used as a marker for prediction of metastasis in HNSCC.