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CXCR4 expression in tumor associated cells in blood is prognostic for progression and survival in pancreatic cancer

The aggressive nature and metastatic potential of pancreatic cancer (PC) results in poor prognosis and high mortality. A better understanding of the underlying biology of PC and the ability of tumor cells to spread to distant sites is needed to advance the treatment of PC. The chemokine receptor CXC...

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Autores principales: Gardner, Kirby P., Tsai, Susan, Aldakkak, Mohammed, Gironda, Stephen, Adams, Daniel L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903256/
https://www.ncbi.nlm.nih.gov/pubmed/35259193
http://dx.doi.org/10.1371/journal.pone.0264763
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author Gardner, Kirby P.
Tsai, Susan
Aldakkak, Mohammed
Gironda, Stephen
Adams, Daniel L.
author_facet Gardner, Kirby P.
Tsai, Susan
Aldakkak, Mohammed
Gironda, Stephen
Adams, Daniel L.
author_sort Gardner, Kirby P.
collection PubMed
description The aggressive nature and metastatic potential of pancreatic cancer (PC) results in poor prognosis and high mortality. A better understanding of the underlying biology of PC and the ability of tumor cells to spread to distant sites is needed to advance the treatment of PC. The chemokine receptor CXCR4 has been heavily implicated in the spread and mobility of many solid cancers based on its role in cancer cell chemotaxis as well as increased metastatic potential. To better elucidate CXCR4’s role in the metastatic spread of PC, we examined its expression on various tumor associated cells (TACs) in the peripheral blood of PC patients, including circulating tumor cells (CTCs), epithelial to mesenchymal transition cells (EMTs), and cancer associated macrophage-like cells (CAMLs). In this pilot study, blood samples were procured from 30 PC patients prior to the start of therapeutic intent. CXCR4 expression was analyzed on TACs captured from the blood samples and evaluated in relation to cell migration as well as patient clinical outcomes. In total, CTCs, EMTs, and CAMLs were found in 27%, 60%, and 97% of PC patients, respectively. High CXCR4 expression in CTCs, CAMLs, and EMTs was found to significantly relate to their increased numbers in circulation. Further, higher expression of CXCR4 in CAMLs and EMTs was significantly related to faster progression and worse survival. These data suggest that CXCR4 expression in PC is strongly related to the intravasation and presence of TACs into circulation, as well as being a possible biomarker for aggressive metastatic disease.
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spelling pubmed-89032562022-03-09 CXCR4 expression in tumor associated cells in blood is prognostic for progression and survival in pancreatic cancer Gardner, Kirby P. Tsai, Susan Aldakkak, Mohammed Gironda, Stephen Adams, Daniel L. PLoS One Research Article The aggressive nature and metastatic potential of pancreatic cancer (PC) results in poor prognosis and high mortality. A better understanding of the underlying biology of PC and the ability of tumor cells to spread to distant sites is needed to advance the treatment of PC. The chemokine receptor CXCR4 has been heavily implicated in the spread and mobility of many solid cancers based on its role in cancer cell chemotaxis as well as increased metastatic potential. To better elucidate CXCR4’s role in the metastatic spread of PC, we examined its expression on various tumor associated cells (TACs) in the peripheral blood of PC patients, including circulating tumor cells (CTCs), epithelial to mesenchymal transition cells (EMTs), and cancer associated macrophage-like cells (CAMLs). In this pilot study, blood samples were procured from 30 PC patients prior to the start of therapeutic intent. CXCR4 expression was analyzed on TACs captured from the blood samples and evaluated in relation to cell migration as well as patient clinical outcomes. In total, CTCs, EMTs, and CAMLs were found in 27%, 60%, and 97% of PC patients, respectively. High CXCR4 expression in CTCs, CAMLs, and EMTs was found to significantly relate to their increased numbers in circulation. Further, higher expression of CXCR4 in CAMLs and EMTs was significantly related to faster progression and worse survival. These data suggest that CXCR4 expression in PC is strongly related to the intravasation and presence of TACs into circulation, as well as being a possible biomarker for aggressive metastatic disease. Public Library of Science 2022-03-08 /pmc/articles/PMC8903256/ /pubmed/35259193 http://dx.doi.org/10.1371/journal.pone.0264763 Text en © 2022 Gardner et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Gardner, Kirby P.
Tsai, Susan
Aldakkak, Mohammed
Gironda, Stephen
Adams, Daniel L.
CXCR4 expression in tumor associated cells in blood is prognostic for progression and survival in pancreatic cancer
title CXCR4 expression in tumor associated cells in blood is prognostic for progression and survival in pancreatic cancer
title_full CXCR4 expression in tumor associated cells in blood is prognostic for progression and survival in pancreatic cancer
title_fullStr CXCR4 expression in tumor associated cells in blood is prognostic for progression and survival in pancreatic cancer
title_full_unstemmed CXCR4 expression in tumor associated cells in blood is prognostic for progression and survival in pancreatic cancer
title_short CXCR4 expression in tumor associated cells in blood is prognostic for progression and survival in pancreatic cancer
title_sort cxcr4 expression in tumor associated cells in blood is prognostic for progression and survival in pancreatic cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903256/
https://www.ncbi.nlm.nih.gov/pubmed/35259193
http://dx.doi.org/10.1371/journal.pone.0264763
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