Epithelial to Mesenchymal Transition in CTCs from breast cancer patients: MGH paper published in Science

Circulating tumor cells get wanderlust

Science 1 February 2013: 
Vol. 339 no. 6119 pp. 580-584DOI:10.1126/science.1228522
Key highlights of the paper:

• Both mesenchymal & epithelial markers were expressed  in rare primary tumor cells but mesenchymal cells were highly enriched in CTCs. 
• An association of mesenchymal CTCs with disease progression was observed by serial monitoring of 11 patients
• Reversible shifts between these epithelial & mesenchymal cell fates accompanied each cycle of response to therapy and disease progression in an index patient
• Provides evidence of EMT in human breast cancer specimens, both in rare cells within primary tumors and more abundantly in CTCs. 
• The researchers found a striking association between expression of mesenchymal markers and clusters of CTCs, rather than single migratory cells.
• The proposal that mesenchymal transformation of epithelial cells is mediated by TGF-β released from platelets is supported by the researchers who note of strong TGF-β signatures in mesenchymal CTC clusters, many of which carry attached platelets
• human primary breast tumors contain rare cancer cells that coexpress mesenchymal and epithelial markers

Methods used:
Herringbone chip using an antibody cocktail (EpCAM, EGFR and Her2). Dual-colorimetric RNA–in situ hybridization (ISH) assay was used to examine tumor cells for expression of  epithelial (E) transcripts: [keratins (KRT) 5, 7, 8, 18, and 19; EpCAM (epithelial cell adhesion molecule); and CDH1 (cadherin 1)] and mesenchymal (M) transcripts: [FN1 (fibronectin 1), CDH2 (cadherin 2), and SERPINE1/PAI1 (serpin peptidase inhibitor, clade E)].