Abstract
Various experimental studies indicate potential involvement of bone marrow (BM)-derived stem cells (SCs) in malignancy development and progression. In this study, we comprehensively analysed systemic trafficking of various populations of BM-derived SCs (BMSCs), i.e., mesenchymal, haematopoietic, endothelial stem/progenitor cells (MSCs, HSCs, EPCs respectively), and of recently discovered population of very small embryonic/epiblast-like SCs (VSELs) in pancreatic cancer patients. Circulating CD133+/Lin−/CD45−/CD34+ cells enriched for HSCs, CD105+/STRO-1+/CD45− cells enriched for MSCs, CD34+/KDR+/CD31+/CD45− cells enriched for EPCs and small CXCR4+CD34+CD133+ subsets of Lin−CD45− cells that correspond to VSELs were enumerated and sorted from blood samples derived from 29 patients with pancreatic cancer, and 19 healthy controls. In addition, plasma levels of stromal-derived factor-1 (SDF-1), growth/inhibitory factors and sphingosine-1-phosphate (S1P; chemoattractants for SCs), as well as, of complement cascade (CC) molecules (C3a, C5a and C5b-9/membrane attack complex – MAC) were measured. Higher numbers of circulating VSELs and MSCs were detected in pancreatic cancer patients (P < 0.05 and 0.01 respectively). This trafficking of BMSCs was associated with significantly elevated C5a (P < 0.05) and C5b-9/MAC (P < 0.005) levels together with S1P concentrations detected in plasma of cancer patients, and seemed to be executed in a SDF-1 independent manner. In conclusion, we demonstrated that in patients with pancreatic cancer, intensified peripheral trafficking of selected populations of BMSCs occurs. This phenomenon seems to correlate with systemic activation of the CC, hepatocyte growth factor and S1P levels. In contrast to previous studies, we demonstrate herein that systemic SDF-1 levels do not seem to be linked with increased mobilization of stem cells in patients with pancreatic cancer.
Highlights
Pancreatic cancer constantly remains a leading cause of mortality among western societies
While we could establish various significant correlations between absolute numbers of selected populations of circulating stem cells (SCs) and stromal-derived factor-1 (SDF-1) levels in healthy individuals [with very small embryonic/epiblast-like SCs (VSELs) (r = 0.34) and HSCs (r = 0.25), P < 0.05 for both], in patients with pancreatic malignancy such associations were not observed, as well as, SDF-1 levels were comparable between patients suffering from resectable, locally advanced and metastatic disease (Table S1)
In this study, we have comprehensively analysed circulating numbers of various BM-derived SCs (BMSCs) populations in patients suffering from pancreatic cancer, as well as, measured several soluble factors that are responsible for BMSCs mobilization/retention
Summary
Pancreatic cancer constantly remains a leading cause of mortality among western societies. This grieving tendency continues mainly because of constant clinical difficulties in its early detection, as well.
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