Laminin N-terminus α31 (LaNt α31) is an alternative splice isoform derived from the laminin α3 gene. The LaNt α31 protein is enriched around the terminal duct lobular units in normal breast tissue. In the skin and cornea the protein influences epithelial cell migration and tissue remodelling. However, LaNt α31 has never been investigated in a tumour environment. Here we analysed LaNt α31 in invasive ductal carcinoma and determined its contribution to breast carcinoma invasion. LaNt α31 expression and distribution were analysed by immunohistochemistry in human breast tissue biopsy sections and tissue microarrays covering 232 breast cancer samples. This analysis revealed LaNt α31 to be upregulated in 56 % of invasive ductal carcinoma specimens compared with matched normal tissue, and further increased in nodal metastasis compared with the tumour mass in 45 % of samples. 65.8 % of triple negative cases displayed medium to high LaNt α31 expression. To study LaNt α31 function, an adenoviral system was used to induce expression in MCF-7 and MDA-MB-231 cells. Metabolic activity, 2D cell migration, and invasion into collagen hydrogels were not significantly different between LaNt α31 overexpressing cells and control treated cells. However, LaNt α31 overexpressing MDA-MB-231 cells displayed a striking change in their mode of invasion into laminin-containing Matrigel; changing from multicellular streaming to individual cellular-invasion. In agreement with these results, 66.7% of the tumours with the highest LaNt α31 expression were non-cohesive. Together these findings indicate that breast cancer-associated changes in LaNt α31 expression could directly contribute to tumour invasiveness, and that this little-studied protein may become a therapeutic target.

中文翻译：

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层粘连蛋白N末端α31在浸润性导管癌中上调并改变了肿瘤浸润的方式。

层粘连蛋白N末端α31（LaNtα31）是衍生自层粘连蛋白α3基因的另一种剪接异构体。LaNtα31蛋白在正常乳腺组织的末端导管小叶单位周围富集。在皮肤和角膜中，蛋白质会影响上皮细胞迁移和组织重塑。然而，从未在肿瘤环境中研究LaNtα31。在这里，我们分析了浸润性导管癌中的LaNtα31并确定了其对乳腺癌浸润的贡献。LaNtα31的表达和分布通过免疫组织化学分析了人类乳腺组织活检切片和覆盖232个乳腺癌样本的组织微阵列。此分析表明，与匹配的正常组织相比，56％的浸润性导管癌标本中的LaNtα31上调，与45％的样本肿块相比，淋巴结转移进一步增加。65.8％的三阴性病例显示LaNtα31中到高表达。为了研究LaNtα31的功能，使用了腺病毒系统来诱导MCF-7和MDA-MB-231细胞中的表达。LaNtα31过表达的细胞与对照处理的细胞之间的代谢活性，二维细胞迁移以及对胶原水凝胶的入侵没有显着差异。然而，过表达LaNtα31的MDA-MB-231细胞在侵袭含层粘连蛋白的基质胶中的模式发生了惊人的变化。从多细胞流向单个细胞入侵的转变。与这些结果一致，具有最高LaNtα31表达的肿瘤中有66.7％是非粘着性的。