Faculty Opinions recommendation of Early dissemination seeds metastasis in breast cancer.

Abstract

Accumulating data suggest that metastatic dissemination often occurs early during tumour formation, but the mechanisms of early metastatic spread have not yet been addressed. Here, by studying metastasis in a HER2-driven mouse breast cancer model, we show that progesterone-induced signalling triggers migration of cancer cells from early lesions shortly after HER2 activation, but promotes proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by increased HER2 expression and tumour-cell density involving microRNA-mediated progesterone receptor downregulation, and was reversible. Cells from early, low-density lesions displayed more stemness features, migrated more and founded more metastases than cells from dense, advanced tumours. Notably, we found that at least 80% of metastases were derived from early disseminated cancer cells. Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination. PMID: 27974799 Funding information This work was supported by: NCI NIH HHS, United States Grant ID: P30 CA196521 NCI NIH HHS, United States Grant ID: F31 CA183185 NCI NIH HHS, United States Grant ID: R03 CA191430 NCI NIH HHS, United States Grant ID: R01 CA109182 NCI NIH HHS, United States Grant ID: U54 CA163131