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1
Transfection of the mouse ICAM-1 gene into murine neuroblastoma enhances susceptibility to lysis, reduces in vivo tumorigenicity and decreases ICAM-2-dependent killing.将小鼠细胞间黏附分子-1（ICAM-1）基因转染至小鼠神经母细胞瘤中可增强其对裂解的敏感性，降低其体内致瘤性，并减少细胞间黏附分子-2（ICAM-2）依赖性杀伤作用。
Cancer Immunol Immunother. 1994 Feb;38(2):135-41. doi: 10.1007/BF01526209.
2
Role of adhesion molecules in lymphokine-activated killer cell killing of bladder cancer cells: further evidence for a third ligand for leucocyte function-associated antigen-1.黏附分子在淋巴因子激活的杀伤细胞杀伤膀胱癌细胞中的作用：白细胞功能相关抗原-1第三种配体的进一步证据
Immunology. 1992 Jun;76(2):286-91.
3
Increased susceptibility of IFN-gamma-treated neuroblastoma cells to lysis by lymphokine-activated killer cells: participation of ICAM-1 induction on target cells.干扰素-γ处理的神经母细胞瘤细胞对淋巴因子激活的杀伤细胞裂解的敏感性增加：细胞间黏附分子-1在靶细胞上的诱导作用。
Int J Cancer. 1991 Feb 20;47(4):527-32. doi: 10.1002/ijc.2910470410.
4
Modulation of leukemic cell sensitivity to lymphokine-activated killer cytolysis: role of intercellular adhesion molecule-1.白血病细胞对淋巴因子激活的杀伤细胞溶解作用敏感性的调节：细胞间黏附分子-1的作用
Exp Hematol. 1992 Oct;20(9):1072-6.
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Target lysis by human LAK cells is critically dependent upon target binding properties, but LFA-1, LFA-3 and ICAM-1 are not the major adhesion ligands on targets.人LAK细胞介导的靶细胞裂解关键取决于靶细胞的结合特性，但淋巴细胞功能相关抗原-1（LFA-1）、淋巴细胞功能相关抗原-3（LFA-3）和细胞间黏附分子-1（ICAM-1）并非靶细胞上的主要黏附配体。
Int J Cancer. 1991 Feb 1;47(3):473-9. doi: 10.1002/ijc.2910470328.
6
B7-1 expression decreases tumorigenicity and induces partial systemic immunity to murine neuroblastoma deficient in major histocompatibility complex and costimulatory molecules.B7-1表达降低了致瘤性，并诱导对主要组织相容性复合体和共刺激分子缺陷的小鼠神经母细胞瘤产生部分全身免疫。
Cancer Gene Ther. 1995 Mar;2(1):39-46.
7
Expression of the adhesion molecules ICAM-1 and ICAM-2 on tumor cell lines does not correlate with their susceptibility to natural killer cell-mediated cytolysis: evidence for additional ligands for effector cell beta integrins.肿瘤细胞系上黏附分子ICAM-1和ICAM-2的表达与其对自然杀伤细胞介导的细胞溶解的敏感性不相关：效应细胞β整合素存在其他配体的证据。
Eur J Immunol. 1992 Apr;22(4):1069-74. doi: 10.1002/eji.1830220429.
8
Interleukin-2 gene transfer into murine neuroblastoma decreases tumorigenicity and enhances systemic immunity causing regression of preestablished retroperitoneal tumors.将白细胞介素-2基因导入小鼠神经母细胞瘤可降低致瘤性并增强全身免疫力，导致预先建立的腹膜后肿瘤消退。
J Immunother Emphasis Tumor Immunol. 1994 Feb;15(2):81-90. doi: 10.1097/00002371-199402000-00001.
9
Induction of intercellular adhesion molecule 1 on small cell lung carcinoma cell lines by gamma-interferon enhances spontaneous and bispecific anti-CD3 x antitumor antibody-directed lymphokine activated killer cell cytotoxicity.γ干扰素诱导小细胞肺癌细胞系表达细胞间黏附分子1可增强自发的以及双特异性抗CD3×抗肿瘤抗体导向的淋巴因子激活的杀伤细胞的细胞毒性。
Cancer Res. 1992 Sep 15;52(18):4890-4.
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Resistance of HER2/neu-overexpressing tumor targets to lymphokine-activated-killer-cell-mediated lysis: evidence for deficiency of binding and post-binding events.HER2/neu过表达肿瘤靶点对淋巴因子激活的杀伤细胞介导的裂解的抗性：结合及结合后事件缺陷的证据。
Cancer Immunol Immunother. 1993 May;36(5):307-14. doi: 10.1007/BF01741169.

引用本文的文献

1
Serum from mice immunized in the context of Treg inhibition identifies DEK as a neuroblastoma tumor antigen.在Treg抑制背景下免疫的小鼠血清将DEK鉴定为神经母细胞瘤肿瘤抗原。
BMC Immunol. 2007 Mar 30;8:4. doi: 10.1186/1471-2172-8-4.
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Murine CD8 lymphocyte expansion in vitro by artificial antigen-presenting cells expressing CD137L (4-1BBL) is superior to CD28, and CD137L expressed on neuroblastoma expands CD8 tumour-reactive effector cells in vivo.通过表达CD137L（4-1BBL）的人工抗原呈递细胞在体外扩增小鼠CD8淋巴细胞优于CD28，并且神经母细胞瘤上表达的CD137L在体内可扩增CD8肿瘤反应性效应细胞。
Immunology. 2004 May;112(1):105-16. doi: 10.1111/j.1365-2567.2004.01853.x.
3
Increased ICAM-1 expression in transformed human oral epithelial cells: molecular mechanism and functional role in peripheral blood mononuclear cell adhesion and lymphokine-activated-killer cell cytotoxicity.转化的人口腔上皮细胞中细胞间黏附分子-1（ICAM-1）表达增加：在外周血单个核细胞黏附及淋巴因子激活的杀伤细胞细胞毒性中的分子机制及功能作用
Int J Oncol. 2000 Sep;17(3):479-86.
4
All-trans retinoic acid decreases susceptibility of a gastric cancer cell line to lymphokine-activated killer cytotoxicity.全反式维甲酸降低胃癌细胞系对淋巴因子激活的杀伤细胞细胞毒性的敏感性。
Br J Cancer. 1997;75(9):1284-90. doi: 10.1038/bjc.1997.218.

本文引用的文献

1
Retroperitoneal inoculation of murine neuroblastoma results in a reliable model for evaluation of the antitumor immune response.将鼠神经母细胞瘤接种于腹膜后可建立一个用于评估抗肿瘤免疫反应的可靠模型。
J Pediatr Surg. 1994 Apr;29(4):538-42. doi: 10.1016/0022-3468(94)90086-8.
2
Weak HLA and beta 2-microglobulin expression of neuronal cell lines can be modulated by interferon.神经元细胞系中弱的人类白细胞抗原（HLA）和β2-微球蛋白表达可被干扰素调节。
Proc Natl Acad Sci U S A. 1984 Oct;81(20):6476-80. doi: 10.1073/pnas.81.20.6476.
3
Striking paucity of HLA-A, B, C and beta 2-microglobulin on human neuroblastoma cell lines.人类神经母细胞瘤细胞系中HLA - A、B、C及β2 -微球蛋白明显缺乏。
J Immunol. 1983 May;130(5):2471-8.
4
Cloned T lymphocytes and monoclonal antibodies as probes for cell surface molecules active in T cell-mediated cytolysis.克隆的T淋巴细胞和单克隆抗体作为探测T细胞介导的细胞溶解中起作用的细胞表面分子的探针。
Immunol Rev. 1982;68:135-69. doi: 10.1111/j.1600-065x.1982.tb01063.x.
5
Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes.淋巴因子激活的杀伤细胞现象。白细胞介素2激活的自体人外周血淋巴细胞对天然杀伤抗性新鲜实体瘤细胞的杀伤作用。
J Exp Med. 1982 Jun 1;155(6):1823-41. doi: 10.1084/jem.155.6.1823.
6
Isolation of microtubule protein from cultured mouse neuroblastoma cells.从小鼠神经母细胞瘤细胞培养物中分离微管蛋白。
Proc Natl Acad Sci U S A. 1970 Jan;65(1):129-36. doi: 10.1073/pnas.65.1.129.
7
Establishment of functional clonal lines of neurons from mouse neuroblastoma.从小鼠神经母细胞瘤建立功能性神经元克隆系。
Proc Natl Acad Sci U S A. 1969 Sep;64(1):311-5. doi: 10.1073/pnas.64.1.311.
8
A new technique for the assay of infectivity of human adenovirus 5 DNA.一种检测人腺病毒5型DNA感染性的新技术。
Virology. 1973 Apr;52(2):456-67. doi: 10.1016/0042-6822(73)90341-3.
9
Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families.细胞间黏附分子-1的一级结构显示了免疫球蛋白超基因家族成员与整合素超基因家族成员之间的相互作用。
Cell. 1988 Mar 25;52(6):925-33. doi: 10.1016/0092-8674(88)90434-5.
10
ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM.细胞间黏附分子（ICAM）是淋巴细胞功能相关抗原-1（LFA-1）的一种黏附配体，与神经细胞黏附分子（NCAM）同源。
Nature. 1988 Feb 18;331(6157):624-7. doi: 10.1038/331624a0.

将小鼠细胞间黏附分子-1（ICAM-1）基因转染至小鼠神经母细胞瘤中可增强其对裂解的敏感性，降低其体内致瘤性，并减少细胞间黏附分子-2（ICAM-2）依赖性杀伤作用。

Transfection of the mouse ICAM-1 gene into murine neuroblastoma enhances susceptibility to lysis, reduces in vivo tumorigenicity and decreases ICAM-2-dependent killing.

作者信息

Katsanis E, Bausero M A, Xu H, Orchard P J, Xu Z, McIvor R S, Brian A A, Blazar B R

机构信息

Department of Pediatrics, University of Minnesota, Minneapolis 55455.

出版信息

Cancer Immunol Immunother. 1994 Feb;38(2):135-41. doi: 10.1007/BF01526209.

DOI:10.1007/BF01526209
PMID:7905790
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11038452/
Abstract

We determined the expression of intercellular adhesion molecules (ICAM) on neuro-2a cells in order to evaluate whether they were involved in cytolysis of murine neuroblastoma. Fluorescence-activated cell sorting analysis revealed that the control neomycin-resistance-gene-transduced line (neuro-2a/LN) had poor expression of ICAM-1 (mean channel fluorescence, MCF = 3.7). An ICAM-1-positive transfectant of neuro-2a (neuro-2a/ICAM-1+) (MCF = 64.3) was generated to evaluate directly the role of this adhesion molecule in cytolysis. Neuro-2a/ICAM-1+ was more sensitive to LAK killing (69.7% at an effector-to-target ratio of 100:1) compared to neuro-2a/LN (48.6%) (P < 0.001). Blocking of neuro-2a/LN and neuro-2a/ICAM-1+ lysis with anti-ICAM-1 monoclonal antibodies (mAbs) did not account for all the LFA-1-dependent killing. These data indicate that even in neuro-2a/ICAM-1+ cells, other LFA-1 ligands participated in the effector-target interaction. Therefore, we examined these cell lines for ICAM-2 expression. Both neuro-2a/LN and neuro-2a/ICAM-1+ lines expressed ICAM-2 (MCF = 16.4 and 16.5). ICAM-2 accounted for the majority of the LFA-1-dependent killing in the ICAM-1-negative target, neuro-2a/LN, while ICAM-1 played a primary role in the cytolysis of the ICAM-1+ transfectant. Inhibition of lysis in the presence of anti-ICAM-1 and ICAM-2 mAbs was comparable to that seen with the addition of anti-LFA-1 mAb, indicating that other LFA-1 ligands were not involved in this system. ICAM-1 expression was associated with decreased in vivo tumorigenicity, mice inoculated with neuro-2a/ICAM-1+ cells had a significantly longer survival compared to those receiving neuro-2a/LN cells (median survival time 35.5 versus 24.5 days) (P < 0.001). It is important to note that ICAM-1 transfection of murine neuroblastoma did not alter its metastatic potential. We conclude that transfection of mouse neuroblastoma with ICAM-1 increases its sensitivity to in vitro lysis and reduces its in vivo tumorigenicity. In ICAM-1-negative murine neuroblastoma cells, ICAM-2 plays a primary role in cell-mediated lysis.

摘要

我们测定了神经母细胞瘤细胞（Neuro-2a）上细胞间黏附分子（ICAM）的表达，以评估它们是否参与小鼠神经母细胞瘤的细胞溶解过程。荧光激活细胞分选分析显示，对照新霉素抗性基因转导细胞系（Neuro-2a/LN）ICAM-1表达水平较低（平均通道荧光强度，MCF = 3.7）。我们构建了Neuro-2a的ICAM-1阳性转染细胞系（Neuro-2a/ICAM-1+）（MCF = 64.3），以直接评估这种黏附分子在细胞溶解中的作用。与Neuro-2a/LN（48.6%）相比，Neuro-2a/ICAM-1+对LAK杀伤更敏感（效应细胞与靶细胞比例为100:1时，杀伤率为69.7%）（P < 0.001）。用抗ICAM-1单克隆抗体（mAb）阻断Neuro-2a/LN和Neuro-2a/ICAM-1+的细胞溶解作用，并未完全消除依赖淋巴细胞功能相关抗原-1（LFA-1）的杀伤作用。这些数据表明，即使在Neuro-2a/ICAM-1+细胞中，其他LFA-1配体也参与了效应细胞与靶细胞的相互作用。因此，我们检测了这些细胞系中ICAM-2的表达。Neuro-2a/LN和Neuro-2a/ICAM-1+细胞系均表达ICAM-2（MCF分别为16.4和16.5）。在ICAM-1阴性靶细胞Neuro-2a/LN中，ICAM-2在依赖LFA-1的杀伤作用中占主要部分，而ICAM-1在ICAM-1+转染细胞的细胞溶解中起主要作用。在抗ICAM-1和ICAM-2 mAb存在的情况下，细胞溶解的抑制作用与添加抗LFA-1 mAb时相当，表明该系统中没有其他LFA-1配体参与。ICAM-1的表达与体内致瘤性降低相关，接种Neuro-2a/ICAM-1+细胞的小鼠比接种Neuro-2a/LN细胞的小鼠存活时间显著延长（中位生存时间分别为35.5天和24.5天）（P < 0.001）。需要注意的是，小鼠神经母细胞瘤的ICAM-1转染并未改变其转移潜能。我们得出结论，小鼠神经母细胞瘤转染ICAM-1后，其对体外细胞溶解的敏感性增加，体内致瘤性降低。在ICAM-1阴性的小鼠神经母细胞瘤细胞中，ICAM-2在细胞介导的溶解过程中起主要作用。