Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
Mol Cancer. 2011 Oct 10;10:127. doi: 10.1186/1476-4598-10-127.
The L1 cell adhesion molecule (L1CAM) is potentially involved in epithelial-mesenchymal transition (EMT). EMT marker expression is of prognostic significance in non-small cell lung cancer (NSCLC). The relevance of L1CAM for NSCLC is unclear. We investigated the protein expression of L1CAM in a cohort of NSCLC patients. L1CAM protein expression was correlated with clinico-pathological parameters including survival and markers of epithelial-mesenchymal transition.
L1CAM protein expression was found in 25% of squamous cell carcinomas and 24% of adenocarcinomas and correlated with blood vessel invasion and metastasis (p < 0.05). L1CAM was an independent predictor of survival in a multivariate analysis including pT, pN, and pM category, and tumor differentiation grade. L1CAM expression positively correlated with vimentin, beta-catenin, and slug, but inversely with E-cadherin (all p-values < 0.05). E-cadherin expression was higher in the tumor center than in the tumor periphery, whereas L1CAM and vimentin were expressed at the tumor-stroma interface. In L1CAM-negative A549 cells the L1CAM expression was upregulated and matrigel invasion was increased after stimulation with TGF-beta1. In L1CAM-positive SK-LU-1 and SK-LC-LL cells matrigel invasion was decreased after L1CAM siRNA knockdown.
A subset of NSCLCs with vessel tropism and increased metastasis aberrantly expresses L1CAM. L1CAM is a novel prognostic marker for NSCLCs that is upregulated by EMT induction and appears to be instrumental for enhanced cell invasion.
L1 细胞黏附分子（L1CAM）可能参与上皮-间充质转化（EMT）。 EMT 标志物的表达在非小细胞肺癌（NSCLC）中具有预后意义。 L1CAM 与 NSCLC 的相关性尚不清楚。我们研究了 NSCLC 患者队列中 L1CAM 的蛋白表达。 L1CAM 蛋白表达与包括生存和 EMT 标志物在内的临床病理参数相关。
在鳞状细胞癌和腺癌中分别有 25%和 24%发现 L1CAM 蛋白表达，并且与血管侵犯和转移相关（p<0.05）。在包括 pT、pN 和 pM 分类以及肿瘤分化程度的多变量分析中，L1CAM 是生存的独立预测因子。 L1CAM 表达与波形蛋白、β-连环蛋白和 slug 呈正相关，但与 E-钙黏蛋白呈负相关（所有 p 值<0.05）。 E-钙黏蛋白在肿瘤中心的表达高于肿瘤周围，而 L1CAM 和波形蛋白在肿瘤-基质界面表达。在 L1CAM 阴性的 A549 细胞中，L1CAM 表达上调，TGF-β1 刺激后基质胶侵袭增加。在 L1CAM 阳性的 SK-LU-1 和 SK-LC-LL 细胞中，L1CAM siRNA 敲低后基质胶侵袭减少。
具有血管趋向性和转移增加的 NSCLC 的一个亚群异常表达 L1CAM。 L1CAM 是 NSCLC 的一个新的预后标志物，它通过 EMT 诱导而上调，并似乎对增强细胞侵袭起重要作用。
