Newman J Robert, Bohannon Isaac A, Zhang Wenyue, Skipper Joni B, Grizzle William E, Rosenthal Eben L
Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Alabama at Birmingham, USA.
Arch Otolaryngol Head Neck Surg. 2008 Nov;134(11):1218-24. doi: 10.1001/archotol.134.11.1218.
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.
研究细胞外基质金属蛋白酶诱导剂（EMMPRIN）缺失是否会在体内抑制头颈部鳞状细胞癌（HNSCC）肿瘤细胞系的生长。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，而基质金属蛋白酶可调节肿瘤细胞的侵袭、生长和血管生成。
使用FaDu肿瘤异种移植的体内研究。
学术研究机构。
严重联合免疫缺陷（SCID）小鼠。
将HNSCC细胞系FaDu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）进行转染。将肿瘤细胞与成纤维细胞结合后异种移植到SCID小鼠的侧腹。在4周内每两周测量一次肿瘤大小，此时处死小鼠，并对肿瘤样本进行增殖（Ki-67免疫组织化学分析）、血管生成（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]检测）分析。
经基因工程改造以表达不同水平EMMPRIN的头颈部癌细胞系的生长情况。
肿瘤生长与EMMPRIN表达增加呈正相关，动物存活率与之呈负相关。与FaDu肿瘤相比，FaDu/E肿瘤在4周时生长明显更大（P = 0.006）。同样，对照载体转染的FaDu肿瘤明显大于FaDu/siE（P < 0.001）。免疫组织化学分析显示，EMMPRIN转染细胞中Ki-67增加，各组之间的凋亡率无显著变化。血管密度和肿瘤形成率也随EMMPRIN表达而显著增加。
本研究表明，靶向抗EMMPRIN治疗可能是HNSCC的一种新的治疗选择。
