Circulating Bone Marrow-Derived Stem Cells In Patients With Pancreatic Cancer

200 Background: Various experimental studies suggest that bone marrow-derived stem cells (BMSCs) may be involved in the development and progression of pancreatic cancer. However, these observations require further studies, and delineation of exact mechanisms responsible for mobilization of BMSCs from the bone marrow to peripheral blood. Methods: A total of 23 patients with newly diagnosed pancreatic cancer (17 with distal metastases) and 15 healthy individuals were recruited to this study. Using fluorescence-activated cell sorter circulating hematopoietic (HSPCs), mesenchymal (MSCs), endothelial (EPCs), and very small embryonic/epiblast-like stem cells (VSELs) were enumerated and sorted. Plasma levels of various growth/inhibitory factors (hepatocyte [HGF], vascular-endothelial [VEGF], leukemia [LIF]), stem cells’ chemoattractants (stromal-derived factor-1 [SDF-1], sphingosine-1-phosphate [S1P]), and complement molecules (anaphylatoxins [C3a, C5a] and complexes [C5b-9/MAC]) were measured. Results: Significantly higher numbers of circulating VSELs and MSCs were detected in pancreatic cancer patients (in both p<0.05), while the numbers of circulating HSPCs and EPCs were comparable between the analyzed groups. Among analyzed biochemical and immunomodulatory factors, levels of C5a, C5b-9/MAC, HGF and S1P, but not of SDF-1, LIF nor VEGF were associated with observed mobilization of BMSCs. Conclusions: In patients with pancreatic cancer selective mobilization of BMSCs from the bone marrow to peripheral blood is observed. This seems to be strongly associated with increased levels of immunomodulatory substances. Our study also highlights that it is S1P and HGF but not SDF-1 that seem to be associated with BMSCs mobilization from the bone marrow to peripheral blood in patients with pancreatic cancer. (MNiSW grant 402 423038).