Laminin N-terminus [alpha]31 is upregulated in invasive ductal breast cancer and changes the mode of tumour invasion

Laminin N-terminus [alpha]31 (LaNt [alpha]31) is an alternative splice isoform derived from the laminin [alpha]3 gene. The LaNt [alpha]31 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 [alpha]31 has never been investigated in a tumour environment. Here we analysed LaNt [alpha]31 in invasive ductal carcinoma and determined its contribution to breast carcinoma invasion. LaNt [alpha]31 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 [alpha]31 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 [alpha]31 expression. To study LaNt [alpha]31 function, an adenoviral system was used to induce expression in MCF-7 and MDA-MB-231 cells. 2D cell migration and invasion into collagen hydrogels were not significantly different between LaNt [alpha]31 overexpressing cells and control treated cells. However, LaNt [alpha]31 overexpression reduced the proliferation rate of MCF-7 and MDA-MB-231 cells. Moreover, LaNt [alpha]31 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 [alpha]31 expression were non-cohesive. Together these findings indicate that breast cancer-associated changes in LaNt [alpha]31 expression could contribute to the processes involved in tumour invasion and may represent a new therapeutic target.