title: An intensified systemic trafficking of bone marrow-derived stem/progenitor cells in patients with pancreatic cancer.
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.
authors.affiliation: Department of Gastroenterology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Teresa
authors.initials: T
authors.lastname: Starzyńska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Dąbkowski
authors.forename: Wojciech
authors.initials: W
authors.lastname: Błogowski
authors.forename: Ewa
authors.initials: E
authors.lastname: Zuba-Surma
authors.forename: Marta
authors.initials: M
authors.lastname: Budkowska
authors.forename: Daria
authors.initials: D
authors.lastname: Sałata
authors.forename: Barbara
authors.initials: B
authors.lastname: Dołęgowska
authors.forename: Wojciech
authors.initials: W
authors.lastname: Marlicz
authors.forename: Jerzy
authors.initials: J
authors.lastname: Lubikowski
authors.forename: Mariusz Z
authors.initials: MZ
authors.lastname: Ratajczak
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology*; D016022:Case-Control Studies; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000235:genetics / Q000276:immunology; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000473:pathology*; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D003165:Complement System Proteins; D013110:Sphingosine