S100A9 is a novel ligand of EMMPRIN that promotes melanoma metastasis

Toshihiko Hibino, Masakiyo Sakaguchi, Shoko Miyamoto, Mami Yamamoto, Akira Motoyama, Junichi Hosoi, Tadashi Shimokata, Tomonobu Ito, Ryoji Tsuboi, Nam Ho Huh

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

The calcium-binding proteins S100A8 and S100A9 can dimerize to form calprotectin, the release of which during tissue damage has been implicated in inflammation and metastasis. However, receptor(s) mediating the physiologic and pathophysiologic effects of this damage-associated "danger signal" are uncertain. In this study, searching for candidate calprotectin receptors by affinity isolation-mass spectrometry, we identified the cell surface glycoprotein EMMPRIN/BASIGIN (CD147/BSG). EMMPRIN specifically bound to S100A9 but not S100A8. Induction of cytokines and matrix metalloproteases (MMP) by S100A9 was markedly downregulated in melanoma cells by attenuation of EMMPRIN. We found that EMMPRIN signaling used the TNF receptor-associated factor TRAF2 distinct from the known S100-binding signaling pathway mediated by RAGE (AGER). S100A9 strongly promoted migration when EMMPRIN was highly expressed, independent of RAGE, whereas EMMPRIN blockade suppressed migration by S100A9. Immunohistologic analysis of melanomas revealed that EMMPRIN was expressed at both the invasive edge of lesions and the adjacent epidermis, where S100A9 was also strongly expressed. In epidermal-specific transgenic mice, tail vein-injected melanoma accumulated in skin expressing S100A9 but not S100A8. Together, our results establish EMMPRIN as a receptor for S100A9 and suggest the therapeutic use in targeting S100A9-EMMPRIN interactions.

Original languageEnglish
Pages (from-to)172-183
Number of pages12
JournalCancer Research
Volume73
Issue number1
DOIs
Publication statusPublished - Jan 1 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'S100A9 is a novel ligand of EMMPRIN that promotes melanoma metastasis'. Together they form a unique fingerprint.

Cite this