Epithelial-to-Mesenchymal Transition Gene Signature in Circulating Melanoma Cells: Biological and Clinical Relevance

Author:

Rapanotti Maria Cristina12,Cugini Elisa2,Campione Elena3,Di Raimondo Cosimo3ORCID,Costanza Gaetana2ORCID,Rossi Piero4,Ferlosio Amedeo1,Bernardini Sergio2,Orlandi Augusto1ORCID,De Luca Anastasia5ORCID,Bianchi Luca3ORCID

Affiliation:

1. Department of Anatomic Pathology, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy

2. Department of Laboratory Medicine, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy

3. Dermatology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy

4. Surgery Division, Department of Surgery Sciences, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy

5. Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, Italy

Abstract

The most promising method for monitoring patients with minimal morbidity is the detection of circulating melanoma cells (CMCs). We have shown that CD45−CD146+ABCB5+ CMCs identify a rare primitive stem/mesenchymal CMCs population associated with disease progression. The epithelial-to-mesenchymal transition (EMT) confers cancer cells a hybrid epithelial/mesenchymal phenotype promoting metastatization. Thus, we investigated the potential clinical value of the EMT gene signature of these primitive CMCs. A reliable quantitative real-time polymerase chain reaction (qRT-PCR) protocol was settled up using tumor cell lines RNA dilutions. Afterwards, immune-magnetically isolated CMCs from advanced melanoma patients, at onset and at the first checkpoint (following immune or targeted therapy), were tested for the level of EMT hallmarks and EMT transcription factor genes. Despite the small cohort of patients, we obtained promising results. Indeed, we observed a deep gene rewiring of the EMT investigated genes: in particular we found that the EMT gene signature of isolated CMCs correlated with patients’ clinical outcomes. In conclusion, We established a reliable qRT-PCR protocol with high sensitivity and specificity to characterize the gene expression of isolated CMCs. To our knowledge, this is the first evidence demonstrating the impact of immune or targeted therapies on EMT hallmark gene expressions in CMCs from advanced melanoma patients.

Funder

University of Rome Tor Vergata

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference106 articles.

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3. Multistep nature of metastatic inefficiency: Dormancy of solitary cells after successful extravasation and limited survival of early micrometastases;Luzzi;Am. J. Pathol.,1998

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5. Adhesion, migration and communication in melanocytes and melanoma;Haass;Pigment. Cell Res.,2005

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