Effect of an anti-human Co-029/tspan8 mouse monoclonal antibody on tumor growth in a nude mouse model.
Effect of an anti-human Co-029/tspan8 mouse monoclonal antibody on tumor growth in a nude mouse model.
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DOI：
10.3389/fphys.2014.00364
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发表时间：
2014
影响因子：
4
通讯作者：
Boucheix C
中科院分区：
文献类型：
--
作者：
Ailane N;Greco C;Zhu Y;Sala-Valdés M;Billard M;Casal I;Bawa O;Opolon P;Rubinstein E;Boucheix C
消化道肿瘤需要新的治疗药物。Co-029/tspan 8是一种在人结直肠肿瘤中高表达的四跨膜蛋白。本文报道了以Co-029/tspan 8为靶点的单克隆抗体Ts29.2对结直肠肿瘤细胞的作用。HT 29、Isreco 1和SW 480结肠直肠肿瘤细胞系用于本研究。HT 29具有Co-029/tspan 8的强内源性表达，而Isreco 1细胞不表达Co-029/tspan 8，SW 480仅具有弱表达。将Isco 1和SW 480转导以表达与HT 29相同水平的Co-029/tspan 8。为了检查单克隆抗体Ts29.2的作用的特异性，将低Co-029/tspan 8表达的SW 480细胞与转导的细胞同时注射到小鼠的背部、左侧和右侧。在早期治疗中，Ts29.2 mAb抑制表达Co-029/tspan 8的肿瘤生长高达70%，而延迟治疗的效率较低。在体外没有检测到抗体对细胞增殖或凋亡诱导的影响。在体内没有观察到活化的半胱天冬酶3标记的增加，并且在处理的小鼠和对照组之间，血管占据的面积没有显著差异。这表明Ts29.2的作用既不与细胞毒性有关，也不与先前报道的Co-029/tspan 8的血管生成特性的抑制有关。通过Ts29.2处理的小鼠的HT 29肿瘤中有丝分裂指数的降低证明了体内细胞增殖的抑制。细胞增殖的体外和体内数据之间的差异表明，Ts29.2与肿瘤细胞的结合可能会改变它们对微环境发出的信号的反应。考虑到四跨膜蛋白Co-029/tspan 8的组织表达的受限模式，这些初步结果提出了在进一步的治疗应用研究中考虑该四跨膜蛋白的抗体靶向。
New therapeutic agents are needed in digestive tract tumors. Co-029/tspan8 is a tetraspanin frequently expressed on human colorectal tumors, In this work, we report the effects of the monoclonal antibody Ts29.2, targeting Co-029/tspan8, on colorectal tumor cells in vitro and after implantation in nude mice. HT29, Isreco1 and SW480 colorectal tumor cell lines were used for this study. HT29 has a strong endogenous expression of Co-029/tspan8, whereas Isreco1 cells don't express Co-029/tspan8 and SW480 has only a weak expression. Isreco1 and SW480 were transduced to express Co-029/tspan8 at the same level as HT29. In order to check the specificity of the effect of monoclonal antibody Ts29.2, low Co-029/tspan8 expressing SW480 cells were injected simultaneously with transduced cells in the back, on the left and right sides of the mice. With an early treatment, Ts29.2 mAb inhibited growth of tumors expressing Co-029/tspan8 up to 70%, whereas a delayed treatment was less efficient. No effect of the antibody on cell proliferation or apoptosis induction was detected in vitro. No increase of activated caspase 3 labeling was observed in vivo and areas occupied by vessels were not significantly different between treated mice and controls. This suggests that the action of Ts29.2 is linked neither to cellular toxicity nor to the inhibition of the previously reported angiogenic properties of Co-029/tspan8. An inhibition of cell proliferation in vivo is demonstrated by a reduction of the mitotic index in HT29 tumors of Ts29.2 treated mice. The discrepancy between in vitro and in vivo data on cell proliferation suggests that the binding of Ts29.2 to tumor cells may modify their response to signals issued from the microenvironment. Given the restricted pattern of tissue expression of the tetraspanin Co-029/tspan8, these preliminary results put forth for consideration the antibody targeting of this tetraspanin in further investigations for therapeutic applications.
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DOI：
10.1084/jem.177.5.1231
发表时间：
1993-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ikeyama S;Koyama M;Yamaoko M;Sasada R;Miyake M
通讯作者：
Miyake M
影响因子：
6
作者：
Huang, CI;Kohno, N;Miyake, M
通讯作者：
Miyake, M
影响因子：
6.4
作者：
Kohno, M;Hasegawa, H;Fujita, S
通讯作者：
Fujita, S
DOI：
10.1073/pnas.81.11.3506
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
ADAMS, DO;HALL, T;KOPROWSKI, H
通讯作者：
KOPROWSKI, H
影响因子：
158.5
作者：
KAMINSKI, MS;ZASADNY, KR;WAHL, RL
通讯作者：
WAHL, RL