Abstract
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.
Highlights
Pancreatic cancer (PC) has one of the highest incidences of mortality, ranking third in the United States with an estimated 45,050 deaths in 2020 [1]
As the intravasation of circulating tumor cell (CTCs), CAMLs, & epithelial to mesenchymal transition cells (EMTs) into circulation has been associated with faster progression and greater metastatic potential, we evaluated the motility receptor CXCR4 expression on these three populations of cells based on their presence in blood, as well as their association with progression free survival (PFS) and overall survival (OS)
When PANC-1 cells were exposed to isoproterenol for 15 minutes, it was observed that CXCR4 expression dropped to an average intensity of 78 (Fig 2A), with much of the signal appearing localized to the nucleus of the cell (Fig 2D and 2E)
Summary
Pancreatic cancer (PC) has one of the highest incidences of mortality, ranking third in the United States with an estimated 45,050 deaths in 2020 [1]. PC is projected to rise to the second leading cause of cancer related mortality in the United States by the year 2030 [2]. A partial cause of the high mortality is the metastatic potential of PC, which is initiated via circulating tumor cell’s (CTCs) ability to spread to distant sites [3, 4]. CXCR4 expression in tumor associated cells in blood in pancreatic cancer for authors D.L.A & K.P.G and financial compensation for S.G’s contract employment, but did not have any direct role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript
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