A novel therapeutic strategy with anti-CD9 antibody in gastric cancers
A novel therapeutic strategy with anti-CD9 antibody in gastric cancers
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DOI：
10.1007/s00535-009-0081-3
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发表时间：
2009-09-01
影响因子：
6.3
通讯作者：
Hayashi, Norio
中科院分区：
文献类型：
--
作者：
Nakamoto, Taisei;Murayama, Yoko;Hayashi, Norio
CD 9是四跨膜蛋白的成员，并且已经显示出参与多种细胞活动，例如运动性、细胞信号传导、增殖、粘附和转移。然而，关于CD 9参与原发性肿瘤的发展过程知之甚少。在本研究中，我们研究了抗CD 9单克隆抗体（ALB 6）对人胃癌细胞异种移植物的抗肿瘤作用。在肿瘤可视化后，将动物分配到ALB 6治疗组或对照IgG治疗组（100 μ g/体/次，静脉内，每周三次。第一周的第1、4和7天）。然后每天监测肿瘤体积。5-溴-2 '-脱氧尿苷（BrdU）免疫组化染色检测肿瘤增殖，末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记（TUNEL）法检测凋亡，CD 34阳性内皮细胞计数检测血管生成。（1，682 +/- A 683 mm（3）与4，507 +/- A 1，012 mm（3）; P = 0.049），BrdU标记指数显著降低（10.9 +/- A 1.1%对17.2 +/- A 1.4%; P = 0.009），凋亡指数显著增加（1.98 +/- A 0.48%对0.72 +/- A 0.09%; P = 0.034），肿瘤微血管密度显著抑制（671，922 +/- A 34，505像素/mm（2）对1，135，043 +/- A 36，086像素/mm（2）; P = 0.037）。这些结果表明，给予抗-CD 9抗体对荷人胃癌细胞的小鼠成功地通过抗增殖、促凋亡和抗血管生成作用抑制肿瘤进展。
CD9 is a member of the tetraspanins, and has been shown to be involved in a variety of cellular activities such as motility, cell signaling, proliferation, adhesion, and metastasis. However, very little is known about the involvement of CD9 in the process of development of primary tumors. In the present study, we investigated whether anti-CD9 monoclonal antibody (ALB6) has antitumor effects in human gastric cancer cell xenografts.Human gastric cancer cell lines (MKN-28) (5 x 10(6) cells/animal) were inoculated subcutaneously into the dorsal region of SCID mice (five mice in each group). After a tumor was visualized, animals were assigned to either the ALB6 treatment group or the control IgG treatment group (100 mu g/body/time, intravenous, three times per week. Day 1, 4, and 7 of first week). Then tumor volumes were monitored every day. Proliferation of tumor was analyzed by 5-bromo-2'-deoxyuridine (BrdU) immunostaining, apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) methods, and angiogenesis was assessed by counting the number of CD34-positive endothelial cells.Tumor volume was significantly suppressed (1,682 +/- A 683 mm(3) versus 4,507 +/- A 1,012 mm(3); P = 0.049), the BrdU labeling indexes were significantly decreased (10.9 +/- A 1.1% versus 17.2 +/- A 1.4%; P = 0.009), the apoptotic indexes were significantly increased (1.98 +/- A 0.48% versus 0.72 +/- A 0.09%; P = 0.034), and tumor microvessel densities were significantly suppressed (671,922 +/- A 34,505 pixels/mm(2) versus 1,135,043 +/- A 36,086 pixels/mm(2); P = 0.037) in the ALB6 treatment group compared with the control IgG treatment group.These results suggest that administration of anti-CD9 antibody to mice bearing human gastric cancer cells successfully inhibits tumor progression via antiproliferative, proapoptotic, and antiangiogenetic effects.