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Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination

JJ. Garcés, M. Simicek, M. Vicari, L. Brozova, L. Burgos, R. Bezdekova, D. Alignani, MJ. Calasanz, K. Growkova, I. Goicoechea, X. Agirre, L. Pour, F. Prosper, R. Rios, J. Martinez-Lopez, P. Millacoy, L. Palomera, R. Del Orbe, A. Perez-Montaña, S....

. 2020 ; 34 (2) : 589-603. [pub] 20191008

Language English Country Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc20025245

Grant support
Cancer Research UK - United Kingdom
NV15-29667A MZ0 CEP Register

Digital library NLK
Full text - Article

E-resources Online Full text

NLK ProQuest Central from 2000-01-01 to 1 year ago
Open Access Digital Library from 1997-01-01
Nursing & Allied Health Database (ProQuest) from 2000-01-01 to 1 year ago
Health & Medicine (ProQuest) from 2000-01-01 to 1 year ago
Public Health Database (ProQuest) from 2000-01-01 to 1 year ago

Links

PubMed 31595039
DOI 10.1038/s41375-019-0588-4
Knihovny.cz E-resources

The reason why a few myeloma cells egress from the bone marrow (BM) into peripheral blood (PB) remains unknown. Here, we investigated molecular hallmarks of circulating tumor cells (CTCs) to identify the events leading to myeloma trafficking into the bloodstream. After using next-generation flow to isolate matched CTCs and BM tumor cells from 32 patients, we found high correlation in gene expression at single-cell and bulk levels (r ≥ 0.94, P = 10-16), with only 55 genes differentially expressed between CTCs and BM tumor cells. CTCs overexpressed genes involved in inflammation, hypoxia, or epithelial-mesenchymal transition, whereas genes related with proliferation were downregulated in CTCs. The cancer stem cell marker CD44 was overexpressed in CTCs, and its knockdown significantly reduced migration of MM cells towards SDF1-α and their adhesion to fibronectin. Approximately half (29/55) of genes differentially expressed in CTCs were prognostic in patients with newly-diagnosed myeloma (n = 553; CoMMpass). In a multivariate analysis including the R-ISS, overexpression of CENPF and LGALS1 was significantly associated with inferior survival. Altogether, these results help understanding the presence of CTCs in PB and suggest that hypoxic BM niches together with a pro-inflammatory microenvironment induce an arrest in proliferation, forcing tumor cells to circulate in PB and seek other BM niches to continue growing.

References provided by Crossref.org

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$a Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination / $c JJ. Garcés, M. Simicek, M. Vicari, L. Brozova, L. Burgos, R. Bezdekova, D. Alignani, MJ. Calasanz, K. Growkova, I. Goicoechea, X. Agirre, L. Pour, F. Prosper, R. Rios, J. Martinez-Lopez, P. Millacoy, L. Palomera, R. Del Orbe, A. Perez-Montaña, S. Garate, L. Blanco, M. Lasa, P. Maiso, J. Flores-Montero, L. Sanoja-Flores, Z. Chyra, A. Vdovin, T. Sevcikova, T. Jelinek, C. Botta, H. El Omri, J. Keats, A. Orfao, R. Hajek, JF. San-Miguel, B. Paiva,
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$a The reason why a few myeloma cells egress from the bone marrow (BM) into peripheral blood (PB) remains unknown. Here, we investigated molecular hallmarks of circulating tumor cells (CTCs) to identify the events leading to myeloma trafficking into the bloodstream. After using next-generation flow to isolate matched CTCs and BM tumor cells from 32 patients, we found high correlation in gene expression at single-cell and bulk levels (r ≥ 0.94, P = 10-16), with only 55 genes differentially expressed between CTCs and BM tumor cells. CTCs overexpressed genes involved in inflammation, hypoxia, or epithelial-mesenchymal transition, whereas genes related with proliferation were downregulated in CTCs. The cancer stem cell marker CD44 was overexpressed in CTCs, and its knockdown significantly reduced migration of MM cells towards SDF1-α and their adhesion to fibronectin. Approximately half (29/55) of genes differentially expressed in CTCs were prognostic in patients with newly-diagnosed myeloma (n = 553; CoMMpass). In a multivariate analysis including the R-ISS, overexpression of CENPF and LGALS1 was significantly associated with inferior survival. Altogether, these results help understanding the presence of CTCs in PB and suggest that hypoxic BM niches together with a pro-inflammatory microenvironment induce an arrest in proliferation, forcing tumor cells to circulate in PB and seek other BM niches to continue growing.
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