Loss of membrane-bound serine protease inhibitor HAI-1 induces oral squamous cell carcinoma cells' invasiveness
| Autor: | Yuko Sato, Tsuyoshi Fukushima, Kenji Yorita, Hiroshi Orikawa, Hiroaki Kataoka, Makiko Kawaguchi, Hiroyuki Tanaka, Takashi Baba, Chen-Yong Lin, Sumio Sakoda |
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| Rok vydání: | 2012 |
| Předmět: |
Proteases
animal structures Protease Cell growth medicine.medical_treatment Cell virus diseases Biology Pathology and Forensic Medicine Cell biology stomatognathic diseases medicine.anatomical_structure Cell culture Cancer cell Cancer research medicine biology.protein Matriptase Epithelial–mesenchymal transition |
| Zdroj: | The Journal of Pathology. 228:181-192 |
| ISSN: | 0022-3417 |
| Popis: | A loss of balance between cell membrane-associated proteases and their inhibitors may underlie cancer invasion and metastasis. We analysed the roles of a membrane- associated serine protease inhibitor, HAI-1, in oral squamous cell carcinoma (OSCC). While membranous HAI-1 was widely observed in cancer cells of human OSCC tissues, this was significantly reduced at the infiltrative invasion front. In vitro, HAI-1 was detected in all eight OSCC cell lines examined, in which its cognate membrane protease, matriptase was also expressed. HAI-1 expression knock-down (KD) in OSCC lines, SAS and HSC-3, reduced the growth of both lines in vitro but significantly enhanced SAS tumourigenicity in vivo, which was accompanied by histological changes suggestive of the epithelial-mesenchymal transition. Both HAI-1-KD lines also exhibited significantly enhanced migratory capability, and membrane-associated but not truncated HAI-1 was required to rescue this phenotype. Other OSCC lines (HSC-2, Sa3, Ca9-22) also showed enhanced migration in response to HAI-1 KD. The enhanced migration is partly attributed to dysregulation of matriptase, as simultaneous matriptase KD alleviated the migration of HAI-1-KD cells. HAI-1 deficiency also altered the expression of CD24, S100A4, CCND2 and DUSP6, all of which are involved in tumour progression. While matriptase was involved in the increased CD24 expression associated with HAI-1 deficiency, the protease appeared to be not responsible for the altered expression of other genes. Therefore, a matriptase-independent mechanism for the invasiveness associated with HAI-1 KD is also present. Together, these observations suggest that HAI-1 has a crucial suppressive role in OSCC cell invasiveness. |
| Databáze: | OpenAIRE |
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