Epithelial-Mesenchymal Transition and Stem Cell Markers in Patients with HER2-Positive Metastatic Breast Cancer
A partir d'échantillons de sang périphérique prélevé sur 28 patientes atteintes d'un cancer du sein métastatique HER2+ traité à l'aide de trastuzumab, cette étude évalue la présence de marqueurs d'une transition épithélio-mésenchymateuse dans les cellules tumorales circulantes et de marqueurs des cellules souches cancéreuses
Currently, there is extensive information about circulating tumor cells (CTCs) and their prognostic value; however, little is known about other characteristics of these cells. In this prospective study, we assessed the gene transcripts of epithelial-to-mesenchymal transition inducing transcription factors (EMT-TFs) and cancer stem cell features in HER2+ metastatic breast cancer (MBC) patients. Epithelial cells were enriched from peripheral blood mononuclear cells (PBMCs) using antibody-coated anti-CD326 antibody (CD326+) magnetic beads, and the residual CD326- PBMCs were further depleted of leukocytes using anti-CD45 antibody-coated magnetic beads (CD326-CD45-). RNA was extracted from all cell fractions, reverse transcribed to cDNA, and subjected to quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to detect EMT-TFs (TWIST1, SNAIL1, ZEB1, and TG2) as a measure of CTCs undergoing EMT (EMT-CTCs). Additionally, PBMCs were analyzed using multi-parameter flow cytometry for ALDH activity and cancer stem cells (CSCs) that express CD24, CD44, and CD133. Twenty-eight patients were included in this study. At least one EMT-TF mRNA was elevated in the CTCs of 88.2% of patients and in the CD326-CD45- cell fraction of 60.7% of patients. The CD326-CD45- fraction of patients with elevated SNAIL1 and ZEB1 transcripts also had a higher percentage of ALDH+/CD133+ cells in their blood than did patients with normal SNAIL1 and ZEB1 expression (P=0.038). Our data indicate that HER2+ MBC patients have EMT-CTCs. Moreover, an enrichment of cancer stem cells was found in CD326-CD45- cells. Additional studies are needed to determine whether EMT-CTCs and CSCs have prognostic value in HER2+ MBC patients treated with trastuzumab-based therapy.
Molecular Cancer Therapeutics , résumé, 2012