Early dissemination seeds metastasis in breast cancer

By Hedayatollah Hosseini, M. Obradović, Martin Hoffmann, K. Harper, M. Sosa, M. Werner-Klein, Lahiri Kanth Nanduri, C. Werno, C. Ehrl, M. Maneck and 17 more. Nature, 2016

647 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/4cc38377c038b5c4ab06f816222ad432bfc29855

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In Cancer Research

1. Zena Werb
2. Pengfei Lu
3. Valerie M. Weaver

In Molecular Biology

1. Hugo Gonzalez
2. Zena Werb
3. C. Hagerling
4. Pengfei Lu
5. M. Egeblad
6. Raghu Kalluri

In Oncology

1. Hugo Gonzalez
2. Zena Werb
3. C. Hagerling
4. Pengfei Lu
5. M. Egeblad
6. Raghu Kalluri
7. Valerie M. Weaver

Citations in the corpus

• Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis (2018, background): “It has been speculated that the latent phase of breast tumorigenesis may include the spread of breast cancer cells at an early, pre-symptomatic stage of primary tumor development when the disseminated cancer cells remain undetected in bone marrow for years before presenting clinically identifiable f”
• Roles of the immune system in cancer: from tumor initiation to metastatic progression (2018, background): “Traditionally, metastasis has been considered to occur in later stages of cancer progression; however, accumulating evidence has also described metastatic dissemination during early tumor formation (Hosseini et al. 2016).”