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Circulating Tumor Cells in Melanoma Patients

Circulating tumor cells (CTCs) are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X) from blood of melanoma patients using a simple centrifu...

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Autores principales: Clawson, Gary A., Kimchi, Eric, Patrick, Susan D., Xin, Ping, Harouaka, Ramdane, Zheng, Siyang, Berg, Arthur, Schell, Todd, Staveley-O’Carroll, Kevin F., Neves, Rogerio I., Mosca, Paul J., Thiboutot, Diane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400630/
https://www.ncbi.nlm.nih.gov/pubmed/22829910
http://dx.doi.org/10.1371/journal.pone.0041052
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author Clawson, Gary A.
Kimchi, Eric
Patrick, Susan D.
Xin, Ping
Harouaka, Ramdane
Zheng, Siyang
Berg, Arthur
Schell, Todd
Staveley-O’Carroll, Kevin F.
Neves, Rogerio I.
Mosca, Paul J.
Thiboutot, Diane
author_facet Clawson, Gary A.
Kimchi, Eric
Patrick, Susan D.
Xin, Ping
Harouaka, Ramdane
Zheng, Siyang
Berg, Arthur
Schell, Todd
Staveley-O’Carroll, Kevin F.
Neves, Rogerio I.
Mosca, Paul J.
Thiboutot, Diane
author_sort Clawson, Gary A.
collection PubMed
description Circulating tumor cells (CTCs) are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X) from blood of melanoma patients using a simple centrifugation device (OncoQuick), and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF) were quantified using QPCR. Approximately one-third of melanoma patients had elevated MIF and MLANA transcripts (p<0.0001 and p<0.001, respectively) compared with healthy controls. In contrast, healthy controls had uniformly higher levels of TYR and MITF than melanoma patients (p<0.0001). There was a marked shift of leukocytes into the CTC-enriched fractions (a 430% increase in RNA recovery, p<0.001), and no relationship between CTC levels and stage of disease was found. CTCs were captured on microfabricated filters and cultured. Captured melanoma CTCs were large cells, and consisted of 2 subpopulations, based on immunoreactivity. One subpopulation (∼50%) stained for both pan-cytokeratin (KRT) markers and the common leukocyte marker CD-45, whereas the second subpopulation stained for only KRT. Since similar cells are described in many cancers, we also examined blood from colorectal and pancreatic cancer patients. We observed analogous results, with most captured CTCs staining for both CD-45/KRT markers (and for the monocyte differentiation marker CD-14). Our results suggest that immature melanocyte-related cells (expressing TYR and MITF RNA) may circulate in healthy controls, although they are not readily detectable without considerable enrichment. Further, as early-stage melanomas develop, immature melanocyte migration into the blood is somehow curtailed, whereas a significant proportion of patients develop elevated CTC levels (based on MIF and MLANA RNAs). The nature of the captured CTCs is consistent with literature describing leukocyte/macrophage-tumor cell fusion hybrids, and their role in metastatic progression.
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spelling pubmed-34006302012-07-24 Circulating Tumor Cells in Melanoma Patients Clawson, Gary A. Kimchi, Eric Patrick, Susan D. Xin, Ping Harouaka, Ramdane Zheng, Siyang Berg, Arthur Schell, Todd Staveley-O’Carroll, Kevin F. Neves, Rogerio I. Mosca, Paul J. Thiboutot, Diane PLoS One Research Article Circulating tumor cells (CTCs) are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X) from blood of melanoma patients using a simple centrifugation device (OncoQuick), and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF) were quantified using QPCR. Approximately one-third of melanoma patients had elevated MIF and MLANA transcripts (p<0.0001 and p<0.001, respectively) compared with healthy controls. In contrast, healthy controls had uniformly higher levels of TYR and MITF than melanoma patients (p<0.0001). There was a marked shift of leukocytes into the CTC-enriched fractions (a 430% increase in RNA recovery, p<0.001), and no relationship between CTC levels and stage of disease was found. CTCs were captured on microfabricated filters and cultured. Captured melanoma CTCs were large cells, and consisted of 2 subpopulations, based on immunoreactivity. One subpopulation (∼50%) stained for both pan-cytokeratin (KRT) markers and the common leukocyte marker CD-45, whereas the second subpopulation stained for only KRT. Since similar cells are described in many cancers, we also examined blood from colorectal and pancreatic cancer patients. We observed analogous results, with most captured CTCs staining for both CD-45/KRT markers (and for the monocyte differentiation marker CD-14). Our results suggest that immature melanocyte-related cells (expressing TYR and MITF RNA) may circulate in healthy controls, although they are not readily detectable without considerable enrichment. Further, as early-stage melanomas develop, immature melanocyte migration into the blood is somehow curtailed, whereas a significant proportion of patients develop elevated CTC levels (based on MIF and MLANA RNAs). The nature of the captured CTCs is consistent with literature describing leukocyte/macrophage-tumor cell fusion hybrids, and their role in metastatic progression. Public Library of Science 2012-07-19 /pmc/articles/PMC3400630/ /pubmed/22829910 http://dx.doi.org/10.1371/journal.pone.0041052 Text en Clawson et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Clawson, Gary A.
Kimchi, Eric
Patrick, Susan D.
Xin, Ping
Harouaka, Ramdane
Zheng, Siyang
Berg, Arthur
Schell, Todd
Staveley-O’Carroll, Kevin F.
Neves, Rogerio I.
Mosca, Paul J.
Thiboutot, Diane
Circulating Tumor Cells in Melanoma Patients
title Circulating Tumor Cells in Melanoma Patients
title_full Circulating Tumor Cells in Melanoma Patients
title_fullStr Circulating Tumor Cells in Melanoma Patients
title_full_unstemmed Circulating Tumor Cells in Melanoma Patients
title_short Circulating Tumor Cells in Melanoma Patients
title_sort circulating tumor cells in melanoma patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400630/
https://www.ncbi.nlm.nih.gov/pubmed/22829910
http://dx.doi.org/10.1371/journal.pone.0041052
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