Stem–Mesenchymal Signature Cell Genes Detected in Heterogeneous Circulating Melanoma Cells Correlate With Disease Stage in Melanoma Patients
During the process of metastasis, cancer cells dissociate from primary tumors, migrate to distal sites, and finally colonize, eventually leading to the formation of metastatic tumors. These cancer cells, defined circulating tumor cells (CTCs) spreading through the blood stream, may develop metastati...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmolb.2020.00092/full |
| _version_ | 1818575886943780864 |
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| author | Maria Cristina Rapanotti Maria Cristina Rapanotti Elena Campione Tara Mayte Suarez Viguria Tara Mayte Suarez Viguria Giulia Spallone Gaetana Costanza Piero Rossi Augusto Orlandi Piera Valenti Sergio Bernardini Luca Bianchi |
| author_facet | Maria Cristina Rapanotti Maria Cristina Rapanotti Elena Campione Tara Mayte Suarez Viguria Tara Mayte Suarez Viguria Giulia Spallone Gaetana Costanza Piero Rossi Augusto Orlandi Piera Valenti Sergio Bernardini Luca Bianchi |
| author_sort | Maria Cristina Rapanotti |
| collection | DOAJ |
| description | During the process of metastasis, cancer cells dissociate from primary tumors, migrate to distal sites, and finally colonize, eventually leading to the formation of metastatic tumors. These cancer cells, defined circulating tumor cells (CTCs) spreading through the blood stream, may develop metastatic lesions or remain dormant. Some emerging clinical evidence supports that some tumor cells may possess metastatic properties already in the earlier stages of tumorigenesis. Because the initiation and progression of vertical growth in human melanoma is fundamental to the notion of tumor virulence and progression, we decided to immune-magnetic collect and molecularly characterize circulating melanoma cells (CMCs) from melanoma patients AJCC staged = pT1b (i.e., transition from radial to vertical phase). CMCs are phenotypically and molecularly heterogeneous, thus we performed a “home-made Liquid-Biopsy,” by targeting the melanoma-associated-antigen, MCAM/MUC18/CD146, and/or the melanoma-initiating marker, ABCB5. We assessed a biomarker qualitative expression panel, contemplating the angiogenic-potential, melanoma-initiating and melanoma-differentiation drivers, cell-cell adhesion molecules, matrix-metallo-proteinases, which was performed on three enriched subpopulations from a total of 61 blood-samples from 21 melanoma patients. At first, a significant differential expression of the specific transcripts was documented between and within the CMC fractions enriched with MCAM-, ABCB5-, and both MCAM/ABCB5-coated beads, when analyzing two distinct groups: early AJCC- (stage I–II) and advanced- staged patients (stage II–IV). Moreover, in the early-AJCC staged-group, we could distinguish “endothelial,” CD45–MCAM+ enriched-, “stem” S-CMCs, CD45–ABCB5+ enriched- and a third hybrid bi-phenotypic CD45–MCAM+/ABCB5+ enriched-fractions, due to three distinct gene-expression profiles. In particular, the endothelial-CMCs were characterized by positive expression of genes involved in migration and invasion, whilst the stem CMC-fraction only expressed stem and differentiation markers. The third subpopulation isolated based on concurrent MCAM and ABCB5 protein expression showed an invasive phenotype. All three distinct CMCs sub-populations, exhibited a primitive, “stem-mesenchymal” profile suggesting a highly aggressive and metastasizing phenotype. This study confirms the phenotypic and molecular heterogeneity observed in melanoma and highlights those putative genes involved in early melanoma spreading and disease progression. |
| first_indexed | 2024-12-15T00:47:13Z |
| format | Article |
| id | doaj.art-8cfc0d06530744d190e111a3d4edb3e0 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-12-15T00:47:13Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-8cfc0d06530744d190e111a3d4edb3e02022-12-21T22:41:31ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2020-05-01710.3389/fmolb.2020.00092534123Stem–Mesenchymal Signature Cell Genes Detected in Heterogeneous Circulating Melanoma Cells Correlate With Disease Stage in Melanoma PatientsMaria Cristina Rapanotti0Maria Cristina Rapanotti1Elena Campione2Tara Mayte Suarez Viguria3Tara Mayte Suarez Viguria4Giulia Spallone5Gaetana Costanza6Piero Rossi7Augusto Orlandi8Piera Valenti9Sergio Bernardini10Luca Bianchi11Department of Onco-Haematology, Tor Vergata University of Rome, Rome, ItalyDepartment of Experimental Medicine, Tor Vergata University of Rome, Rome, ItalyDepartment of Dermatology, Tor Vergata University of Rome, Rome, ItalyDepartment of Onco-Haematology, Tor Vergata University of Rome, Rome, ItalyDepartment of Experimental Medicine, Tor Vergata University of Rome, Rome, ItalyDepartment of Dermatology, Tor Vergata University of Rome, Rome, ItalyAnatomic Pathology Division, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, ItalySurgery Division, Department of Systems Medicine, Tor Vergata University of Rome, Rome, ItalyAnatomic Pathology Division, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, ItalyDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, ItalyDepartment of Experimental Medicine, Tor Vergata University of Rome, Rome, ItalyDepartment of Dermatology, Tor Vergata University of Rome, Rome, ItalyDuring the process of metastasis, cancer cells dissociate from primary tumors, migrate to distal sites, and finally colonize, eventually leading to the formation of metastatic tumors. These cancer cells, defined circulating tumor cells (CTCs) spreading through the blood stream, may develop metastatic lesions or remain dormant. Some emerging clinical evidence supports that some tumor cells may possess metastatic properties already in the earlier stages of tumorigenesis. Because the initiation and progression of vertical growth in human melanoma is fundamental to the notion of tumor virulence and progression, we decided to immune-magnetic collect and molecularly characterize circulating melanoma cells (CMCs) from melanoma patients AJCC staged = pT1b (i.e., transition from radial to vertical phase). CMCs are phenotypically and molecularly heterogeneous, thus we performed a “home-made Liquid-Biopsy,” by targeting the melanoma-associated-antigen, MCAM/MUC18/CD146, and/or the melanoma-initiating marker, ABCB5. We assessed a biomarker qualitative expression panel, contemplating the angiogenic-potential, melanoma-initiating and melanoma-differentiation drivers, cell-cell adhesion molecules, matrix-metallo-proteinases, which was performed on three enriched subpopulations from a total of 61 blood-samples from 21 melanoma patients. At first, a significant differential expression of the specific transcripts was documented between and within the CMC fractions enriched with MCAM-, ABCB5-, and both MCAM/ABCB5-coated beads, when analyzing two distinct groups: early AJCC- (stage I–II) and advanced- staged patients (stage II–IV). Moreover, in the early-AJCC staged-group, we could distinguish “endothelial,” CD45–MCAM+ enriched-, “stem” S-CMCs, CD45–ABCB5+ enriched- and a third hybrid bi-phenotypic CD45–MCAM+/ABCB5+ enriched-fractions, due to three distinct gene-expression profiles. In particular, the endothelial-CMCs were characterized by positive expression of genes involved in migration and invasion, whilst the stem CMC-fraction only expressed stem and differentiation markers. The third subpopulation isolated based on concurrent MCAM and ABCB5 protein expression showed an invasive phenotype. All three distinct CMCs sub-populations, exhibited a primitive, “stem-mesenchymal” profile suggesting a highly aggressive and metastasizing phenotype. This study confirms the phenotypic and molecular heterogeneity observed in melanoma and highlights those putative genes involved in early melanoma spreading and disease progression.https://www.frontiersin.org/article/10.3389/fmolb.2020.00092/fullliquid biopsycirculating melanoma cellsMCAM/MUC18/CD146ABCB5gene-expression panelmelanoma disease progression |
| spellingShingle | Maria Cristina Rapanotti Maria Cristina Rapanotti Elena Campione Tara Mayte Suarez Viguria Tara Mayte Suarez Viguria Giulia Spallone Gaetana Costanza Piero Rossi Augusto Orlandi Piera Valenti Sergio Bernardini Luca Bianchi Stem–Mesenchymal Signature Cell Genes Detected in Heterogeneous Circulating Melanoma Cells Correlate With Disease Stage in Melanoma Patients Frontiers in Molecular Biosciences liquid biopsy circulating melanoma cells MCAM/MUC18/CD146 ABCB5 gene-expression panel melanoma disease progression |
| title | Stem–Mesenchymal Signature Cell Genes Detected in Heterogeneous Circulating Melanoma Cells Correlate With Disease Stage in Melanoma Patients |
| title_full | Stem–Mesenchymal Signature Cell Genes Detected in Heterogeneous Circulating Melanoma Cells Correlate With Disease Stage in Melanoma Patients |
| title_fullStr | Stem–Mesenchymal Signature Cell Genes Detected in Heterogeneous Circulating Melanoma Cells Correlate With Disease Stage in Melanoma Patients |
| title_full_unstemmed | Stem–Mesenchymal Signature Cell Genes Detected in Heterogeneous Circulating Melanoma Cells Correlate With Disease Stage in Melanoma Patients |
| title_short | Stem–Mesenchymal Signature Cell Genes Detected in Heterogeneous Circulating Melanoma Cells Correlate With Disease Stage in Melanoma Patients |
| title_sort | stem mesenchymal signature cell genes detected in heterogeneous circulating melanoma cells correlate with disease stage in melanoma patients |
| topic | liquid biopsy circulating melanoma cells MCAM/MUC18/CD146 ABCB5 gene-expression panel melanoma disease progression |
| url | https://www.frontiersin.org/article/10.3389/fmolb.2020.00092/full |
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