アブストラクト(45巻1号:神奈川歯学)

神奈川歯学

Japanese

Title : 免疫や血管・リンパ管新生阻害による癌の進展制御
Subtitle : 神奈川歯科大学学会 第44回総会宿題報告
Authors : 松本剛一
Authors(kana) :
Organization : 神奈川歯科大学顎顔面外科学講座
Journal : 神奈川歯学
Volume : 45
Number : 1
Page : 38-42
Year/Month : 2010 / 6
Article : 報告
Publisher : 神奈川歯科大学学会
Abstract : 「1. キラー細胞の標的細胞認識における細胞間接着分子LFA-1の必要性」生体は自然免疫と獲得免疫を用いることで癌を排除あるいは癌の増殖を抑制すると考えられている. 生体内に癌細胞が発生すると, 生体はさまざまな仕組みで癌細胞を排除しようとする. 自然免疫もその仕組みの1つと考えられている. 癌に対する自然免疫とは, NK細胞, NKT細胞, γδT細胞, 好中球, マクロファージなどの原始的細胞が癌細胞を攻撃, 排除する初期対応を指す. 自己と非自己の判別は各細胞が主要組織適合遺伝子複合体(MHC)クラスIと呼ばれる分子を介して提示した抗原ペプチドを識別することよって行われる. 細胞障害性T細胞(CTL)は獲得免疫の主役を演じる細胞であり, 癌細胞を認識し効率的にこれを排除すると考えられている. しかし, 人に発生する癌の多くは自然発生癌であるため癌細胞の抗原性は低く, 多くの場合CTLによっては排除されにくいということも事実である.
Practice : 歯科学
Keywords : LFA-1, NK細胞, NKT細胞, CSDA

English

Title : Control of Cancer Progression by Immunity, Antiangiogenesis and Antilymphangiogenesis
Subtitle :
Authors : Goichi MATSUMOTO
Authors(kana) :
Organization : Department of Oral and Maxillofacial Surgery, Kanagawa Dental College
Journal : Kanagawa Shigaku
Volume : 45
Number : 1
Page : 38-42
Year/Month : 2010 / 6
Article : Report
Publisher : Kanagawa Odontological Society
Abstract : [Abstract] IL-2-activated NK cells exhibit cytotoxic activity against a wide variety of tumor cells in a non-MHC-restricted fashion and in the absence of prior sensitization. The molecular mechanisms that regulate the cytotoxicity and attachment of activated killer cells to tumor target cells are not known. We provide genetic evidence in LFA-1-/- mice that the cell adhesion receptors LFA-1 regulates the cytotoxic activity of IL-2-activated NK cells against a variety of different tumor cells. LFA-1-/- IL-2-activated NK cells showed impaired binding and conjugate formation with target cells. These results provide the first genetic evidence of the role of adhesion receptors in IL-2-activated NK killing. Interleukin 12 (IL-12)-activated NKT and NK cells exhibit cytotoxic activity against a wide variety of tumor cells in the absence of prior sensitization. Here we demonstrate that the integrin adhesion receptor LFA-1 (CD11a/CD18) regulates the cytotoxic activity of IL-12-activated NKT and NK cells against YAC-1 and EL-4 tumor cells. LFA-1-/- IL-12-activated NKT and NK cells showed impaired conjugate formation with target cells. NKT cells produce large amounts of cytokines associated with both the Th1 (IFN-γ) and Th2 (IL-4) responses following stimulation of α-galactosylceramide (α-GalCer) remains unclear. Intriguingly, LFA-1-/- mice showed increased IL-4 and polarized Th2-type responses in response to α-GalCer in vitro and in vivo. Cold shock domain protein A (CSDA) is a DNA-binding protein that represses angiogenesis by directly binding to hypoxia response element. We used the cell line NR-S1M, a mouse SCC model with a high rate of lymphnode metastasis. Into these cells we transfected the expression-plasmid coding for mouse CSDA. We showed that overexpression of CSDA significantly inhibits the production of VEGF-A in NR-S1M cells. The overexpression of CSDA in NR-S1M cells inhibited tumor growth, inhibited regional lymph-node metastasis, and reduced the density of blood vessels and lymphatic vessels in the primary tumors in vivo.
Practice : Dentistry
Keywords : LFA-1, CSDA