Modulation of tumor cell growth in vivo by extracellular matrix metalloprotease inducer.
Modulation of tumor cell growth in vivo by extracellular matrix metalloprotease inducer.
复制标题
DOI：
10.1001/archotol.134.11.1218
复制
发表时间：
2008-11
影响因子：
--
通讯作者：
Rosenthal, Eben L.
中科院分区：
文献类型：
--
作者：
Newman, J. Robert;Bohannon, Isaac A.;Zhang, Wenyue;Skipper, Joni B.;Grizzle, William E.;Rosenthal, Eben L.
探讨细胞外基质金属蛋白酶诱导因子（EMMPRIN）缺失是否会抑制头颈部鳞状细胞癌（HNSCC）肿瘤细胞株的体内生长。肿瘤细胞来源的EMMPRIN在HNSCC中高度过表达，并且被认为是由周围的成纤维细胞诱导以刺激基质金属蛋白酶，其调节肿瘤细胞侵袭、生长和血管生成。使用FaDu肿瘤异种移植物的体内研究。学术研究设施。严重联合免疫缺陷（SCID）小鼠。用EMMPRIN（FaDu/E）、对照载体（FaDu）或表达针对EMMPRIN的小干扰RNA的质粒（FaDu/siE）转染HNSCC细胞系FaDu。将肿瘤细胞与成纤维细胞组合异种移植到SCID小鼠的侧腹上。在4周内每两周测量一次肿瘤，此时处死小鼠，并分析肿瘤样品的增殖（Ki-67免疫组织化学分析）、血管形成（因子VIII染色）和凋亡（TUNEL [末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸-生物素缺口末端标记]测定）。头颈部癌细胞系的生长基因工程表达可变水平的EMMPRIN。肿瘤生长与EMMPRIN表达增加呈正相关，动物存活率与EMMPRIN表达增加负相关。与FaDu肿瘤相比，FaDu/E肿瘤生长在4周时显著更大（P = .006）。类似地，对照载体转染的FaDu肿瘤显著大于FaDu/siE（P<.001）。免疫组化分析表明，增加Ki-67在EMMPRIN转染细胞，没有显着变化的凋亡率组之间。血管密度和肿瘤形成率也显著增加EMMPRIN表达。这项研究表明，抗EMMPRIN靶向治疗可能被证明是HNSCC的一种新的治疗选择。
To investigate if loss of extracellular matrix metalloprotease inducer (EMMPRIN) will inhibit the growth of head and neck squamous cell carcinoma (HNSCC) tumor cell lines in vivo. Tumor cell–derived EMMPRIN is highly overexpressed in HNSCC and is thought to be induced by surrounding fibroblasts to stimulate matrix metalloproteases, which modulate tumor cell invasion, growth, and angiogenesis. In vivo study using FaDu tumor xenografts. Academic research facility. Severe combined immunodeficiency (SCID) mice. The HNSCC cell line FaDu was transfected with EMMPRIN (FaDu/E), control vector (FaDu), or plasmid-expressing small-interfering RNA against EMMPRIN (FaDu/siE). Tumor cells combined with fibroblast cells were xenografted onto the flank of SCID mice. Tumors were measured biweekly over 4 weeks, at which time the mice were killed, and tumor samples were analyzed for proliferation (Ki-67 immunohistochemical analysis), vascularization (factor VIII staining), and apoptosis (TUNEL [terminal deoxynucleotidyl transferase– mediated deoxyuridine triphosphate–biotin nick end labeling] assay). Growth of head and neck cancer cell lines genetically engineered to express variable levels of EMMPRIN. Tumor growth positively correlated and animal survival negatively correlated with increasing EMMPRIN expression. FaDu/E tumor growth was significantly larger at 4 weeks compared with FaDu tumors (P = .006). Similarly, the control vector–transfected FaDu tumors were significantly larger than FaDu/siE (P<.001). Immunohistochemical analysis demonstrated increased Ki-67 in EMMPRIN-transfected cells, without a significant change in the rate of apoptosis between groups. Vascular density and tumor formation rate also increased significantly with EMMPRIN expression. This study suggests that anti-EMMPRIN– targeted therapy may prove to be a novel treatment option in HNSCC.
登录
查看更多内容
影响因子：
3.6
作者：
Vigneswaran, N;Beckers, S;Zacharias, W
通讯作者：
Zacharias, W
影响因子：
2.6
作者：
Rosenthal, Eben L.;Vidrine, D. Macy;Zhang, Wenyue
通讯作者：
Zhang, Wenyue
影响因子：
11.2
作者：
Tang, Y;Nakada, MT;Yan, L
通讯作者：
Yan, L
影响因子：
2.6
作者：
Rosenthal, EL;Shreenivas, S;Gladson, CL
通讯作者：
Gladson, CL
影响因子：
6.7
作者：
Yan, L;Zucker, S;Toole, BR
通讯作者：
Toole, BR