Takashi Shinomiya

Interleukin‐21 triggers both cellular and humoral immune responses leading to therapeutic antitumor effects against head and neck squamous cell carcinoma

Interleukin‐21 (IL‐21) plays important roles in the regulation of T, B, and natural killer (NK) cells. We hypothesized that the cytokine may provide a novel immunotherapy strategy for cancer by stimulating both Th1 and Th2 immune responses. In this context, antitumor immunity induced by IL‐21 was examined in mice bearing subcutaneous head and neck squamous cell carcinomas (HNSCC).

Activation of pro-MMP-2 mediated by MT1-MMP in human salivary gland carcinomas: possible regulation of pro-MMP-2 activation by TIMP-2

Matrix metalloproteinases (MMPs), a family of extracellular matrix‐degrading enzymes, are considered to play important roles in cancer invasion and metastasis. The present study examined the production levels of eight different MMPs (MMP‐1, 2, 3, 7, 8, 9 and 13, and MT1‐MMP) and two tissue inhibitors of metalloproteinases (TIMP‐1 and 2) in homogenates of human salivary gland carcinomas [mucoepidermoid carcinomas (MECs), adenoid cystic carcinomas (ACCs), and adenocarcinomas (ADEs)] and non‐neoplastic control salivary glands using sandwich enzyme immunoassay systems. The levels of MMP‐1, MMP‐2, MMP‐13, MT1‐MMP, and TIMP‐1 were significantly higher in the carcinoma samples than in the controls (p < 0.05). Gelatin zymography demonstrated that the activation ratio of the MMP‐2 zymogen (pro‐MMP‐2) was significantly higher in the carcinomas than in the controls (p < 0.05). In addition, the activation ratio in MECs was significantly higher than that in ACCs or ADEs (p < 0.01) and also correlated with histological grade and lymph node metastasis in MECs (p < 0.05), whereas the ratio showed no such correlation in ACCs or ADEs. Although the production levels of pro‐MMP‐2 and MT1‐MMP were similar among these carcinoma groups, TIMP‐2 levels were significantly higher in ACCs and ADEs than in MECs (p < 0.01). In carcinoma samples, the pro‐MMP‐2 activation ratio correlated directly with the MT1‐MMP/TIMP‐2 ratio (r = 0.736, n = 23; p < 0.01). Immunohistochemistry and in situ zymography demonstrated localization of MMP‐2, MT1‐MMP, and TIMP‐2 to carcinoma cells, but only in MECs did carcinoma cell nests exhibit gelatinolytic activity, which was inhibited by 1,10‐phenanthroline. These results suggest that enhanced activation of pro‐MMP‐2 mediated by MT1‐MMP is implicated in the invasion and metastasis of MECs and that TIMP‐2 may regulate pro‐MMP‐2 activation in salivary gland carcinomas. Copyright