The Role of N-Cadherin in Breast Cancer Metastasis

Abstract

Abstract : N-cadherin is expressed in highly invasive tumor cell lines which lack E-cadnerin expression. We transfected a weakly-metastatic and E-cadherin expressing breast cancer cell line, MCF-7, with N-cadherin and analyzed the effects on cell migration, invasion and metastasis. N-cadherin expressing cells migrated more efficiently and showed increased invasion of Matrigel. All cells produced low levels of the matrix metalloproteinase MMP-9 which was dramatically up-regulated by treatment with FGF-2 only in N-cadnerin expressing cells. Migration and invasion of Matrigel were also greatly enhanced by this treatment. When injected into the mammary fat pad of nude mice, N-cadnerin expressing cells, but not control MCF-7 cells, metastasized widely to various organs. The expression of both E- and N-cadnerin was maintained both in the primary tumors and metastatic lesions. These results demonstrate that N-cadherin promotes motility, invasion and metastasis even in the presence of the normally suppressive E-cadherin. The increase in MMP-9 production by N- cadherin expressing cells in response to a growth factor may endow them with a greater ability to penetrate matrix protein barriers, while the increase in their adherence to endothelium may improve their ability to enter and exit the vasculature, two properties that may be responsible for metastasis of N-cadherin expressing cells.