Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination
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...
Gespeichert in:
| Veröffentlicht in: | Leukemia 2020-02, Vol.34 (2), p.589-603 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 603 |
|---|---|
| container_issue | 2 |
| container_start_page | 589 |
| container_title | Leukemia |
| container_volume | 34 |
| creator | Garcés, Juan-Jose Simicek, Michal Vicari, Marco Brozova, Lucie Burgos, Leire Bezdekova, Renata Alignani, Diego Calasanz, Maria-Jose Growkova, Katerina Goicoechea, Ibai Agirre, Xabier Pour, Ludek Prosper, Felipe Rios, Rafael Martinez-Lopez, Joaquin Millacoy, Pamela Palomera, Luis Del Orbe, Rafael Perez-Montaña, Albert Garate, Sonia Blanco, Laura Lasa, Marta Maiso, Patricia Flores-Montero, Juan Sanoja-Flores, Luzalba Chyra, Zuzana Vdovin, Alexander Sevcikova, Tereza Jelinek, Tomas Botta, Cirino El Omri, Halima Keats, Jonathan Orfao, Alberto Hajek, Roman San-Miguel, Jesus F. Paiva, Bruno |
| description | 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. |
| doi_str_mv | 10.1038/s41375-019-0588-4 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2303204153</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A612927094</galeid><sourcerecordid>A612927094</sourcerecordid><originalsourceid>FETCH-LOGICAL-c564t-89e67dc470944aaab45c7d84dac284ebd23c8f1b7d16fd143f13f51836d0d6793</originalsourceid><addsrcrecordid>eNp9kk1rFTEUhoMo9lr9AW4kIIibqfmcybgrxS8ouKnrkJucuU3JJNdkhnL_vQm3WisqWRzCed4c3pMXoZeUnFHC1bsiKB9kR-jYEalUJx6hDRVD30kp6WO0IUoNXT8ycYKelXJDSGv2T9EJp3KUhI8bdLjKJhab_X7xKZqA9zlNPvi4w2nC1me7BrO067LOKWMLIRTsI57XsPh9ADwfIKTZvMcGR7jFc3IQ8JLwGh3kspjosPMFTIFWC8w-mjbrOXoymVDgxV09Rd8-fri6-Nxdfv305eL8srOyF0unRugHZ8VARiGMMVsh7eCUcMYyJWDrGLdqotvB0X5yVPCJ8klSxXtHXD-M_BS9Pb5bnX1foSx69qXZMBHSWjTjhDMiqOQVff0HepPWXLdSKTFIQhkX7L8UFyMdhBrlPbUzAbSPU1qysW20Pu8pG1kzVKmzv1D1uLonmyLUv4CHgje_Ca7BhOW6pLC2jZaHID2CNqdSMkx6n_1s8kFTolt69DE9uqZHt_Topnl152zdzuB-KX7GpQLsCJTaijvI99b__eoPrtPOJQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2349174895</pqid></control><display><type>article</type><title>Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination</title><source>MEDLINE</source><source>SpringerLink_现刊</source><creator>Garcés, Juan-Jose ; Simicek, Michal ; Vicari, Marco ; Brozova, Lucie ; Burgos, Leire ; Bezdekova, Renata ; Alignani, Diego ; Calasanz, Maria-Jose ; Growkova, Katerina ; Goicoechea, Ibai ; Agirre, Xabier ; Pour, Ludek ; Prosper, Felipe ; Rios, Rafael ; Martinez-Lopez, Joaquin ; Millacoy, Pamela ; Palomera, Luis ; Del Orbe, Rafael ; Perez-Montaña, Albert ; Garate, Sonia ; Blanco, Laura ; Lasa, Marta ; Maiso, Patricia ; Flores-Montero, Juan ; Sanoja-Flores, Luzalba ; Chyra, Zuzana ; Vdovin, Alexander ; Sevcikova, Tereza ; Jelinek, Tomas ; Botta, Cirino ; El Omri, Halima ; Keats, Jonathan ; Orfao, Alberto ; Hajek, Roman ; San-Miguel, Jesus F. ; Paiva, Bruno</creator><creatorcontrib>Garcés, Juan-Jose ; Simicek, Michal ; Vicari, Marco ; Brozova, Lucie ; Burgos, Leire ; Bezdekova, Renata ; Alignani, Diego ; Calasanz, Maria-Jose ; Growkova, Katerina ; Goicoechea, Ibai ; Agirre, Xabier ; Pour, Ludek ; Prosper, Felipe ; Rios, Rafael ; Martinez-Lopez, Joaquin ; Millacoy, Pamela ; Palomera, Luis ; Del Orbe, Rafael ; Perez-Montaña, Albert ; Garate, Sonia ; Blanco, Laura ; Lasa, Marta ; Maiso, Patricia ; Flores-Montero, Juan ; Sanoja-Flores, Luzalba ; Chyra, Zuzana ; Vdovin, Alexander ; Sevcikova, Tereza ; Jelinek, Tomas ; Botta, Cirino ; El Omri, Halima ; Keats, Jonathan ; Orfao, Alberto ; Hajek, Roman ; San-Miguel, Jesus F. ; Paiva, Bruno</creatorcontrib><description>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.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/s41375-019-0588-4</identifier><identifier>PMID: 31595039</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>38/39 ; 38/91 ; 631/67/1990/804 ; 631/67/68 ; Analysis ; Blood circulation ; Bone marrow ; Bone Marrow - pathology ; Cancer Research ; CD44 antigen ; Cell Line, Tumor ; Cell migration ; Cell Movement - genetics ; Cell proliferation ; Cell Proliferation - genetics ; Critical Care Medicine ; Egress ; Epithelial-Mesenchymal Transition - genetics ; Fibronectin ; Fibronectins ; Gene expression ; Gene Expression - genetics ; Genes ; Genetic aspects ; Genetic transcription ; Hematology ; Humans ; Hypoxia ; Hypoxia - genetics ; Hypoxia - pathology ; Inflammation ; Inflammation - genetics ; Inflammation - pathology ; Intensive ; Internal Medicine ; Medicine ; Medicine & Public Health ; Mesenchyme ; Metastasis ; Microenvironments ; Multiple myeloma ; Multiple Myeloma - genetics ; Multiple Myeloma - pathology ; Multivariate analysis ; Neoplastic Cells, Circulating - pathology ; Neoplastic Stem Cells - pathology ; Oncology ; Peripheral blood ; Prognosis ; SDF-1 protein ; Stem cells ; Transcription ; Transcription, Genetic - genetics ; Tumor cells ; Tumor Microenvironment - genetics ; Tumors</subject><ispartof>Leukemia, 2020-02, Vol.34 (2), p.589-603</ispartof><rights>The Author(s), under exclusive licence to Springer Nature Limited 2019</rights><rights>COPYRIGHT 2020 Nature Publishing Group</rights><rights>2019© The Author(s), under exclusive licence to Springer Nature Limited 2019</rights><rights>The Author(s), under exclusive licence to Springer Nature Limited 2019.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c564t-89e67dc470944aaab45c7d84dac284ebd23c8f1b7d16fd143f13f51836d0d6793</citedby><cites>FETCH-LOGICAL-c564t-89e67dc470944aaab45c7d84dac284ebd23c8f1b7d16fd143f13f51836d0d6793</cites><orcidid>0000-0001-6115-8790 ; 0000-0001-9235-4671 ; 0000-0003-4375-7399 ; 0000-0002-1522-4504 ; 0000-0002-1240-1958</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41375-019-0588-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41375-019-0588-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31595039$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Garcés, Juan-Jose</creatorcontrib><creatorcontrib>Simicek, Michal</creatorcontrib><creatorcontrib>Vicari, Marco</creatorcontrib><creatorcontrib>Brozova, Lucie</creatorcontrib><creatorcontrib>Burgos, Leire</creatorcontrib><creatorcontrib>Bezdekova, Renata</creatorcontrib><creatorcontrib>Alignani, Diego</creatorcontrib><creatorcontrib>Calasanz, Maria-Jose</creatorcontrib><creatorcontrib>Growkova, Katerina</creatorcontrib><creatorcontrib>Goicoechea, Ibai</creatorcontrib><creatorcontrib>Agirre, Xabier</creatorcontrib><creatorcontrib>Pour, Ludek</creatorcontrib><creatorcontrib>Prosper, Felipe</creatorcontrib><creatorcontrib>Rios, Rafael</creatorcontrib><creatorcontrib>Martinez-Lopez, Joaquin</creatorcontrib><creatorcontrib>Millacoy, Pamela</creatorcontrib><creatorcontrib>Palomera, Luis</creatorcontrib><creatorcontrib>Del Orbe, Rafael</creatorcontrib><creatorcontrib>Perez-Montaña, Albert</creatorcontrib><creatorcontrib>Garate, Sonia</creatorcontrib><creatorcontrib>Blanco, Laura</creatorcontrib><creatorcontrib>Lasa, Marta</creatorcontrib><creatorcontrib>Maiso, Patricia</creatorcontrib><creatorcontrib>Flores-Montero, Juan</creatorcontrib><creatorcontrib>Sanoja-Flores, Luzalba</creatorcontrib><creatorcontrib>Chyra, Zuzana</creatorcontrib><creatorcontrib>Vdovin, Alexander</creatorcontrib><creatorcontrib>Sevcikova, Tereza</creatorcontrib><creatorcontrib>Jelinek, Tomas</creatorcontrib><creatorcontrib>Botta, Cirino</creatorcontrib><creatorcontrib>El Omri, Halima</creatorcontrib><creatorcontrib>Keats, Jonathan</creatorcontrib><creatorcontrib>Orfao, Alberto</creatorcontrib><creatorcontrib>Hajek, Roman</creatorcontrib><creatorcontrib>San-Miguel, Jesus F.</creatorcontrib><creatorcontrib>Paiva, Bruno</creatorcontrib><title>Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>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.</description><subject>38/39</subject><subject>38/91</subject><subject>631/67/1990/804</subject><subject>631/67/68</subject><subject>Analysis</subject><subject>Blood circulation</subject><subject>Bone marrow</subject><subject>Bone Marrow - pathology</subject><subject>Cancer Research</subject><subject>CD44 antigen</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Movement - genetics</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - genetics</subject><subject>Critical Care Medicine</subject><subject>Egress</subject><subject>Epithelial-Mesenchymal Transition - genetics</subject><subject>Fibronectin</subject><subject>Fibronectins</subject><subject>Gene expression</subject><subject>Gene Expression - genetics</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic transcription</subject><subject>Hematology</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Hypoxia - genetics</subject><subject>Hypoxia - pathology</subject><subject>Inflammation</subject><subject>Inflammation - genetics</subject><subject>Inflammation - pathology</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mesenchyme</subject><subject>Metastasis</subject><subject>Microenvironments</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - genetics</subject><subject>Multiple Myeloma - pathology</subject><subject>Multivariate analysis</subject><subject>Neoplastic Cells, Circulating - pathology</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Oncology</subject><subject>Peripheral blood</subject><subject>Prognosis</subject><subject>SDF-1 protein</subject><subject>Stem cells</subject><subject>Transcription</subject><subject>Transcription, Genetic - genetics</subject><subject>Tumor cells</subject><subject>Tumor Microenvironment - genetics</subject><subject>Tumors</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kk1rFTEUhoMo9lr9AW4kIIibqfmcybgrxS8ouKnrkJucuU3JJNdkhnL_vQm3WisqWRzCed4c3pMXoZeUnFHC1bsiKB9kR-jYEalUJx6hDRVD30kp6WO0IUoNXT8ycYKelXJDSGv2T9EJp3KUhI8bdLjKJhab_X7xKZqA9zlNPvi4w2nC1me7BrO067LOKWMLIRTsI57XsPh9ADwfIKTZvMcGR7jFc3IQ8JLwGh3kspjosPMFTIFWC8w-mjbrOXoymVDgxV09Rd8-fri6-Nxdfv305eL8srOyF0unRugHZ8VARiGMMVsh7eCUcMYyJWDrGLdqotvB0X5yVPCJ8klSxXtHXD-M_BS9Pb5bnX1foSx69qXZMBHSWjTjhDMiqOQVff0HepPWXLdSKTFIQhkX7L8UFyMdhBrlPbUzAbSPU1qysW20Pu8pG1kzVKmzv1D1uLonmyLUv4CHgje_Ca7BhOW6pLC2jZaHID2CNqdSMkx6n_1s8kFTolt69DE9uqZHt_Topnl152zdzuB-KX7GpQLsCJTaijvI99b__eoPrtPOJQ</recordid><startdate>20200201</startdate><enddate>20200201</enddate><creator>Garcés, Juan-Jose</creator><creator>Simicek, Michal</creator><creator>Vicari, Marco</creator><creator>Brozova, Lucie</creator><creator>Burgos, Leire</creator><creator>Bezdekova, Renata</creator><creator>Alignani, Diego</creator><creator>Calasanz, Maria-Jose</creator><creator>Growkova, Katerina</creator><creator>Goicoechea, Ibai</creator><creator>Agirre, Xabier</creator><creator>Pour, Ludek</creator><creator>Prosper, Felipe</creator><creator>Rios, Rafael</creator><creator>Martinez-Lopez, Joaquin</creator><creator>Millacoy, Pamela</creator><creator>Palomera, Luis</creator><creator>Del Orbe, Rafael</creator><creator>Perez-Montaña, Albert</creator><creator>Garate, Sonia</creator><creator>Blanco, Laura</creator><creator>Lasa, Marta</creator><creator>Maiso, Patricia</creator><creator>Flores-Montero, Juan</creator><creator>Sanoja-Flores, Luzalba</creator><creator>Chyra, Zuzana</creator><creator>Vdovin, Alexander</creator><creator>Sevcikova, Tereza</creator><creator>Jelinek, Tomas</creator><creator>Botta, Cirino</creator><creator>El Omri, Halima</creator><creator>Keats, Jonathan</creator><creator>Orfao, Alberto</creator><creator>Hajek, Roman</creator><creator>San-Miguel, Jesus F.</creator><creator>Paiva, Bruno</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6115-8790</orcidid><orcidid>https://orcid.org/0000-0001-9235-4671</orcidid><orcidid>https://orcid.org/0000-0003-4375-7399</orcidid><orcidid>https://orcid.org/0000-0002-1522-4504</orcidid><orcidid>https://orcid.org/0000-0002-1240-1958</orcidid></search><sort><creationdate>20200201</creationdate><title>Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination</title><author>Garcés, Juan-Jose ; Simicek, Michal ; Vicari, Marco ; Brozova, Lucie ; Burgos, Leire ; Bezdekova, Renata ; Alignani, Diego ; Calasanz, Maria-Jose ; Growkova, Katerina ; Goicoechea, Ibai ; Agirre, Xabier ; Pour, Ludek ; Prosper, Felipe ; Rios, Rafael ; Martinez-Lopez, Joaquin ; Millacoy, Pamela ; Palomera, Luis ; Del Orbe, Rafael ; Perez-Montaña, Albert ; Garate, Sonia ; Blanco, Laura ; Lasa, Marta ; Maiso, Patricia ; Flores-Montero, Juan ; Sanoja-Flores, Luzalba ; Chyra, Zuzana ; Vdovin, Alexander ; Sevcikova, Tereza ; Jelinek, Tomas ; Botta, Cirino ; El Omri, Halima ; Keats, Jonathan ; Orfao, Alberto ; Hajek, Roman ; San-Miguel, Jesus F. ; Paiva, Bruno</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c564t-89e67dc470944aaab45c7d84dac284ebd23c8f1b7d16fd143f13f51836d0d6793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>38/39</topic><topic>38/91</topic><topic>631/67/1990/804</topic><topic>631/67/68</topic><topic>Analysis</topic><topic>Blood circulation</topic><topic>Bone marrow</topic><topic>Bone Marrow - pathology</topic><topic>Cancer Research</topic><topic>CD44 antigen</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Movement - genetics</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - genetics</topic><topic>Critical Care Medicine</topic><topic>Egress</topic><topic>Epithelial-Mesenchymal Transition - genetics</topic><topic>Fibronectin</topic><topic>Fibronectins</topic><topic>Gene expression</topic><topic>Gene Expression - genetics</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic transcription</topic><topic>Hematology</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Hypoxia - genetics</topic><topic>Hypoxia - pathology</topic><topic>Inflammation</topic><topic>Inflammation - genetics</topic><topic>Inflammation - pathology</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mesenchyme</topic><topic>Metastasis</topic><topic>Microenvironments</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - genetics</topic><topic>Multiple Myeloma - pathology</topic><topic>Multivariate analysis</topic><topic>Neoplastic Cells, Circulating - pathology</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Oncology</topic><topic>Peripheral blood</topic><topic>Prognosis</topic><topic>SDF-1 protein</topic><topic>Stem cells</topic><topic>Transcription</topic><topic>Transcription, Genetic - genetics</topic><topic>Tumor cells</topic><topic>Tumor Microenvironment - genetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Garcés, Juan-Jose</creatorcontrib><creatorcontrib>Simicek, Michal</creatorcontrib><creatorcontrib>Vicari, Marco</creatorcontrib><creatorcontrib>Brozova, Lucie</creatorcontrib><creatorcontrib>Burgos, Leire</creatorcontrib><creatorcontrib>Bezdekova, Renata</creatorcontrib><creatorcontrib>Alignani, Diego</creatorcontrib><creatorcontrib>Calasanz, Maria-Jose</creatorcontrib><creatorcontrib>Growkova, Katerina</creatorcontrib><creatorcontrib>Goicoechea, Ibai</creatorcontrib><creatorcontrib>Agirre, Xabier</creatorcontrib><creatorcontrib>Pour, Ludek</creatorcontrib><creatorcontrib>Prosper, Felipe</creatorcontrib><creatorcontrib>Rios, Rafael</creatorcontrib><creatorcontrib>Martinez-Lopez, Joaquin</creatorcontrib><creatorcontrib>Millacoy, Pamela</creatorcontrib><creatorcontrib>Palomera, Luis</creatorcontrib><creatorcontrib>Del Orbe, Rafael</creatorcontrib><creatorcontrib>Perez-Montaña, Albert</creatorcontrib><creatorcontrib>Garate, Sonia</creatorcontrib><creatorcontrib>Blanco, Laura</creatorcontrib><creatorcontrib>Lasa, Marta</creatorcontrib><creatorcontrib>Maiso, Patricia</creatorcontrib><creatorcontrib>Flores-Montero, Juan</creatorcontrib><creatorcontrib>Sanoja-Flores, Luzalba</creatorcontrib><creatorcontrib>Chyra, Zuzana</creatorcontrib><creatorcontrib>Vdovin, Alexander</creatorcontrib><creatorcontrib>Sevcikova, Tereza</creatorcontrib><creatorcontrib>Jelinek, Tomas</creatorcontrib><creatorcontrib>Botta, Cirino</creatorcontrib><creatorcontrib>El Omri, Halima</creatorcontrib><creatorcontrib>Keats, Jonathan</creatorcontrib><creatorcontrib>Orfao, Alberto</creatorcontrib><creatorcontrib>Hajek, Roman</creatorcontrib><creatorcontrib>San-Miguel, Jesus F.</creatorcontrib><creatorcontrib>Paiva, Bruno</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database (ProQuest)</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database (Proquest)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Garcés, Juan-Jose</au><au>Simicek, Michal</au><au>Vicari, Marco</au><au>Brozova, Lucie</au><au>Burgos, Leire</au><au>Bezdekova, Renata</au><au>Alignani, Diego</au><au>Calasanz, Maria-Jose</au><au>Growkova, Katerina</au><au>Goicoechea, Ibai</au><au>Agirre, Xabier</au><au>Pour, Ludek</au><au>Prosper, Felipe</au><au>Rios, Rafael</au><au>Martinez-Lopez, Joaquin</au><au>Millacoy, Pamela</au><au>Palomera, Luis</au><au>Del Orbe, Rafael</au><au>Perez-Montaña, Albert</au><au>Garate, Sonia</au><au>Blanco, Laura</au><au>Lasa, Marta</au><au>Maiso, Patricia</au><au>Flores-Montero, Juan</au><au>Sanoja-Flores, Luzalba</au><au>Chyra, Zuzana</au><au>Vdovin, Alexander</au><au>Sevcikova, Tereza</au><au>Jelinek, Tomas</au><au>Botta, Cirino</au><au>El Omri, Halima</au><au>Keats, Jonathan</au><au>Orfao, Alberto</au><au>Hajek, Roman</au><au>San-Miguel, Jesus F.</au><au>Paiva, Bruno</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2020-02-01</date><risdate>2020</risdate><volume>34</volume><issue>2</issue><spage>589</spage><epage>603</epage><pages>589-603</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31595039</pmid><doi>10.1038/s41375-019-0588-4</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-6115-8790</orcidid><orcidid>https://orcid.org/0000-0001-9235-4671</orcidid><orcidid>https://orcid.org/0000-0003-4375-7399</orcidid><orcidid>https://orcid.org/0000-0002-1522-4504</orcidid><orcidid>https://orcid.org/0000-0002-1240-1958</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2020-02, Vol.34 (2), p.589-603 |
| issn | 0887-6924 1476-5551 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2303204153 |
| source | MEDLINE; SpringerLink_现刊 |
| subjects | 38/39 38/91 631/67/1990/804 631/67/68 Analysis Blood circulation Bone marrow Bone Marrow - pathology Cancer Research CD44 antigen Cell Line, Tumor Cell migration Cell Movement - genetics Cell proliferation Cell Proliferation - genetics Critical Care Medicine Egress Epithelial-Mesenchymal Transition - genetics Fibronectin Fibronectins Gene expression Gene Expression - genetics Genes Genetic aspects Genetic transcription Hematology Humans Hypoxia Hypoxia - genetics Hypoxia - pathology Inflammation Inflammation - genetics Inflammation - pathology Intensive Internal Medicine Medicine Medicine & Public Health Mesenchyme Metastasis Microenvironments Multiple myeloma Multiple Myeloma - genetics Multiple Myeloma - pathology Multivariate analysis Neoplastic Cells, Circulating - pathology Neoplastic Stem Cells - pathology Oncology Peripheral blood Prognosis SDF-1 protein Stem cells Transcription Transcription, Genetic - genetics Tumor cells Tumor Microenvironment - genetics Tumors |
| title | Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T07%3A36%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Transcriptional%20profiling%20of%20circulating%20tumor%20cells%20in%20multiple%20myeloma:%20a%20new%20model%20to%20understand%20disease%20dissemination&rft.jtitle=Leukemia&rft.au=Garc%C3%A9s,%20Juan-Jose&rft.date=2020-02-01&rft.volume=34&rft.issue=2&rft.spage=589&rft.epage=603&rft.pages=589-603&rft.issn=0887-6924&rft.eissn=1476-5551&rft_id=info:doi/10.1038/s41375-019-0588-4&rft_dat=%3Cgale_proqu%3EA612927094%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2349174895&rft_id=info:pmid/31595039&rft_galeid=A612927094&rfr_iscdi=true |