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

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

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Abstract

Background: Periostin, 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) wasidentified as a common up-regulated gene among Periostin, IFITM1 and Wnt-5b overexpressing HNSCC cells by usingmicroarray data sets. In this study, we investigated the roles of MMP-10 in the invasion of HNSCC.Methods and Findings: We 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 ofMMP-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 overexpressioninduced 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.Conclusions: These 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.
Lingua originaleEnglish
Numero di pagine0
RivistaPLoS One
Volume6
Stato di pubblicazionePublished - 2011

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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Campisi, G., Iizuka, S., Qi, G., Siriwardena, S. B. S. M., Tsunematsu, T., Kikuchi, A., Deraz, E. M., Kiekhaee, M. R., Tani, H., Takata, T., Muzio, L. L., Ogawa, I., Obayashi, M., Abiko, Y., Kudo, Y., & Yoshida, M. (2011). MMP-10/stromelysin-2 promotes invasion of head and neck cancer. PLoS One, 6.