Detailed characterization of multiple myeloma circulating tumor cells shows unique phenotypic, cytogenetic, functional, and circadian distribution profile
| Autor: | J M Sayagués, Luis A. Corchete, Ramón García-Sanz, Montserrat Martín, Mercedes Garayoa, Maria-Victoria Mateos, Laura San-Segundo, Jesús F. San Miguel, Teresa Paíno, Enrique M. Ocio, Paloma Bárcena, Bruno Paiva, Alberto Orfao, María-Belén Vidriales, Norma C. Gutiérrez, Irene Aires-Mejia, Maria-Luz Sanchez, Ines Mota, Cristina Jimenez |
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| Rok vydání: | 2013 |
| Předmět: |
Pathology
medicine.medical_specialty Stromal cell Plasma Cells Immunology CD34 Biology CD38 Biochemistry Immunophenotyping Circulating tumor cell Antigens CD medicine Humans Prospective Studies CXC chemokine receptors Tumor Stem Cell Assay medicine.diagnostic_test Cell Cycle Cell Biology Hematology Neoplastic Cells Circulating Prognosis Circadian Rhythm medicine.anatomical_structure Cytogenetic Analysis Cancer research Bone marrow Multiple Myeloma Fluorescence in situ hybridization |
| Zdroj: | Blood. 122:3591-3598 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2013-06-510453 |
| Popis: | Circulating myeloma tumor cells (CTCs) as defined by the presence of peripheral blood (PB) clonal plasma cells (PCs) are a powerful prognostic marker in multiple myeloma (MM). However, the biological features of CTCs and their pathophysiological role in MM remains unexplored. Here, we investigate the phenotypic, cytogenetic, and functional characteristics as well as the circadian distribution of CTCs vs paired bone marrow (BM) clonal PCs from MM patients. Our results show that CTCs typically represent a unique subpopulation of all BM clonal PCs, characterized by downregulation (P < .05) of integrins (CD11a/CD11c/CD29/CD49d/CD49e), adhesion (CD33/CD56/CD117/CD138), and activation molecules (CD28/CD38/CD81). Fluorescence in situ hybridization analysis of fluorescence-activated cell sorter-sorted CTCs also unraveled different cytogenetic profiles vs paired BM clonal PCs. Moreover, CTCs were mostly quiescent and associated with higher clonogenic potential when cocultured with BM stromal cells. Most interestingly, CTCs showed a circadian distribution which fluctuates in a similar pattern to that of CD34(+) cells, and opposite to stromal cell-derived factor 1 plasma levels and corresponding surface expression of CXC chemokine receptor 4 on clonal PCs, suggesting that in MM, CTCs may egress to PB to colonize/metastasize other sites in the BM during the patients' resting period. |
| Databáze: | OpenAIRE |
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