Rosenthal Eben L, Vidrine D Macy, Zhang Wenyue
Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294-0012, USA.
Laryngoscope. 2006 Jul;116(7):1086-92. doi: 10.1097/01.mlg.0000224368.58870.3c.
Extracellular matrix metalloprotease inducer (EMMPRIN) is a molecule expressed on the cell surface of tumor cells that has been shown to induce both tumor cells and fibroblasts to express matrix metalloproteases in vitro. We hypothesize that fibroblasts are stimulated by EMMPRIN to create a microenvironment favorable to tumor growth.
Case series review of laryngeal cancer and assessment of tumor cell lines in vivo.
EMMPRIN immunoreactivity in 33 pathologic specimens from patients with supraglottic laryngeal cancer was correlated with clinicopathologic features and survival. The CAL 27 cell line was transfected with EMMPRIN (CAL 27E) or a control vector (CAL 27). Cells were xenografted into the flank of severe combined immunodeficient (SCID) mice with or without a co-injection of normal dermal fibroblasts (NDFs).
Immunohistochemical detection of EMMPRIN in laryngeal cancer specimens demonstrated expression in all the tumors but not in adjacent, histologically normal mucosa. EMMPRIN membrane immunoreactivity (transmembrane EMMPRIN score) was associated with nodal positivity (P=.07), and it was associated with poorer survival (hazard ratio=2.4, 95% confidence interval 0.88, 6.55). As a categoric variable, higher EMMPRIN expression positively correlates with higher mortality. To determine whether EMMPRIN mediates tumor growth in vivo through fibroblast stimulation, EMMPRIN-expressing CAL 27 (CAL 27E) xenografted (n=20) onto the flank of SCID mice developed larger tumors than CAL 27 control vector transfected cells alone (n=20), but they were not significantly larger (P=.17). However, when CAL 27E cells were co-injected with NDFs, there was a statistically significant increase in tumor growth compared with the CAL 27 cells co-injected with NDFs (n=10, P=.0038).
As a cell surface expressed protein that promotes tumor growth and high expression in head and neck squamous cell carcinoma but not in normal tissue, EMMPRIN may be a good target for directed molecular therapy.
细胞外基质金属蛋白酶诱导剂（EMMPRIN）是一种在肿瘤细胞表面表达的分子，已证实在体外它能诱导肿瘤细胞和成纤维细胞表达基质金属蛋白酶。我们推测成纤维细胞受EMMPRIN刺激后会形成有利于肿瘤生长的微环境。
喉癌病例系列回顾及体内肿瘤细胞系评估。
对33例声门上喉癌患者的病理标本进行EMMPRIN免疫反应性检测，并将其与临床病理特征及生存率相关联。用EMMPRIN（CAL 27E）或对照载体（CAL 27）转染CAL 27细胞系。将细胞接种到重度联合免疫缺陷（SCID）小鼠的侧腹，同时或不同时共注射正常真皮成纤维细胞（NDFs）。
在喉癌标本中通过免疫组织化学检测到EMMPRIN在所有肿瘤中均有表达，但在相邻的组织学正常黏膜中未表达。EMMPRIN膜免疫反应性（跨膜EMMPRIN评分）与淋巴结阳性相关（P = 0.07），且与较差的生存率相关（风险比 = 2.4，95%置信区间0.88，6.55）。作为一个分类变量，较高的EMMPRIN表达与较高的死亡率呈正相关。为了确定EMMPRIN是否通过刺激成纤维细胞在体内介导肿瘤生长，接种到SCID小鼠侧腹的表达EMMPRIN的CAL 27（CAL 27E）（n = 20）形成的肿瘤比单独转染对照载体的CAL 27细胞（n = 20）形成的肿瘤更大，但差异无统计学意义（P = 0.17）。然而，当CAL 27E细胞与NDFs共注射时，与CAL 27细胞与NDFs共注射相比（n = 10，P = 0.0038），肿瘤生长有统计学意义的增加。
作为一种在细胞表面表达、促进肿瘤生长且在头颈部鳞状细胞癌中高表达而在正常组织中不表达的蛋白质，EMMPRIN可能是定向分子治疗的良好靶点。
