Liver surgery induces an immediate mobilization of progenitor cells in liver cancer patients: A potential role for G-CSF.
BACKGROUND
In preclinical models recruitment of bone-marrow derived (endothelial) progenitor cells (BD(E)PCs) contributes to tumor growth and metastasis formation. Here we investigated whether these (E)PCs and mobilizing cytokines are released after partial hepatectomy or radiofrequency ablation (RFA) for liver tumors. In addition, we tested whether G-CSF could play a role in EPC mobilization in mice and in human volunteers.


RESULTS
Patients undergoing partial hepatectomy or RFA showed an instantaneous release of EPCs following laparotomy and mobilization of the liver. Elevated EPC levels were maintained during the entire procedure, but dropped to near-baseline levels 4 h after completion of the procedure. Plasma G-CSF levels showed a 5-10-fold increase after the procedure and low-dose G-CSF administration to mice or healthy volunteers was sufficient to induce an immediate release of EPCs. Surgery also caused an increase in the plasma levels of VEGF, but not SDF-1alpha.


METHODS
Before, during and after liver surgery plasma and mononuclear cells were collected from 12 patients undergoing partial hepatectomy or RFA. To explore the role of G-CSF C57Bl/6 mice and 20 human volunteers received G-CSF (0.3, 3 or 300microg). In all individuals, (E)PC numbers were determined by flow cytometry at predefined timepoints shortly after therapy. Plasma levels of G-CSF, VEGF and SDF-1alpha were measured by ELISA.


CONCLUSIONS
Compliant with previous published data concerning VDA and chemotherapy treatment, liver surgery induces an instantaneous release of EPCs, conceivably in response to elevated G-CSF levels. This suggests the value of exploring therapeutic avenues to prevent this process.
Langenberg
Marlies H G
MH
Department of Medical Oncology, UMC Utrecht, The Netherlands. m.langenberg@umcutrecht.nl
Nijkamp
Maarten W
MW
Roodhart
Jeanine M L
JM
Snoeren
Nikol
N
Tang
Terence
T
Shaked
Yuval
Y
van Hillegersberg
Richard
R
Witteveen
Petronella O
PO
Vermaat
Joost S P
JS
Kranenburg
Onno
O
Kerbel
Robert S
RS
Medema
Rene H
RH
Borel Rinkes
Inne H M
IH
Voest
Emile E
EE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017115:Catheter Ablation; D016207:Cytokines / Q000097:blood; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000097:blood*; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000473:pathology* / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011379:Prognosis; D013234:Stem Cells / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D055815:Young Adult
D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor