Extracellular matrix metalloprotease inducer stimulates fibroblast-mediated tumor growth in vivo
Extracellular matrix metalloprotease inducer stimulates fibroblast-mediated tumor growth in vivo
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DOI：
10.1097/01.mlg.0000224368.58870.3c
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发表时间：
2006-07-01
期刊：
影响因子：
2.6
通讯作者：
Zhang, Wenyue
中科院分区：
文献类型：
--
作者：
Rosenthal, Eben L.;Vidrine, D. Macy;Zhang, Wenyue
假设：细胞外基质金属蛋白酶诱导剂（EMMPRIN）是一种表达于肿瘤细胞表面的分子，已显示其在体外诱导肿瘤细胞和成纤维细胞表达基质金属蛋白酶。我们假设成纤维细胞被EMMPRIN刺激，以创造有利于肿瘤生长的微环境。研究设计.喉癌的病例系列回顾和体内肿瘤细胞系的评估。方法. 33例声门上型喉癌患者的病理标本中EMMPRIN免疫反应性与临床病理特征和生存率相关。用EMMPRIN（CAL 27 E）或对照载体（CAL 27）转染CAL 27细胞系。将细胞异种移植到严重联合免疫缺陷（SCID）小鼠的侧腹中，有或没有正常真皮成纤维细胞（NDF）的共注射。结果EMMPRIN在喉癌标本中的免疫组化检测表明，在所有肿瘤中表达，但在相邻的组织学正常粘膜中不表达。EMMPRIN膜免疫反应性（跨膜EMMPRIN评分）与淋巴结阳性相关（P = 0.07），并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，EMMPRIN表达越高，死亡率越高。为了确定EMMPRIN是否通过成纤维细胞刺激介导体内肿瘤生长，将表达EMMPRIN的CAL 27（CAL 27E）异种移植（n = 20）到SCID小鼠的侧腹上比单独的CAL 27对照载体转染的细胞（n = 20）产生更大的肿瘤，但它们并不显著更大（P = 0.17）。然而，当CAL 27 E细胞与NDF共注射时，与CAL 27细胞与NDF共注射相比，肿瘤生长有统计学显著增加（n = 10，P =.0038）。结论. EMMPRIN作为一种促进肿瘤生长的细胞表面表达蛋白，在头颈部鳞癌中高表达，而在正常组织中不表达，可能成为定向分子治疗的良好靶点。
Hypothesis: 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. Study Design. Case series review of laryngeal cancer and assessment of tumor cell lines in vivo. Methods. 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). Results. 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). Conclusions. 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.