Pilot study to relate clinical outcome in pancreatic carcinoma and angiogenic plasma factors/circulating mature/progenitor endothelial cells: Preliminary results.
Circulating endothelial cells (CEC) and bone marrow-derived endothelial progenitors (ECP) play important roles in tumor growth and have been proposed as non-invasive markers of angiogenesis. However, CEC and ECP levels have not been investigated in pancreatic carcinoma patients. Using four-color flow cytometry procedures, we evaluated the count of resting (rCEC) and activated (aCEC) endothelial cells and ECP in the peripheral blood of pancreatic carcinoma patients before and after chemotherapy, consisting of gemcitabine (GEM) alone or in combination with oxaliplatin (OX), or with 5-fluorouracil (5-FU). We also correlated CEC and ECP levels with plasma levels of relevant angiogenic factors, such as vascular endothelial growth factor (VEGF)-A, VEGF-D, angiopoietin (Angio)-1, and chemokine C-X-C motif ligand (CXCL)12, measured by ELISA, and with clinical features of pancreatic cancer. The aCEC, rCEC, ECP, and VEGF-A plasma levels were significantly higher in locally-advanced and metastatic patients than controls. Both ECP and VEGF-A levels correlated positively with disease stage and inversely with patient's overall survival. Measurements after the treatment course showed that VEGF-A plasma concentrations and ECP counts had decreased significantly. In particular, VEGF-A and rCEC were significantly down after treatment with GEM alone or in combination with OX. No significant differences in terms of circulating angiogenic factor or endothelial cell subtype levels were found between responders (patients entering partial remission or with stable disease) and non-responders (patients with progressive disease). The study provides insights into angiogenesis mechanisms in pancreatic carcinoma, for which anti-angiogenic targeting of VEGF-A and ECP could be of interest.
Department of Clinical Physiopathology, University of Turin, Turin, Italy.
Barbara
B
Vizio
Anna
A
Novarino
Alice
A
Giacobino
Carmen
C
Cristiano
Adriana
A
Prati
Gabriele
G
Brondino
Libero
L
Ciuffreda
Graziella
G
Bellone
D000368:Aged; D042682:Angiopoietins / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D054377:Chemokine CXCL12 / Q000097:blood; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D010865:Pilot Projects; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D042643:Vascular Endothelial Growth Factor D / Q000097:blood; D000093542:Gemcitabine
D042682:Angiopoietins; D054377:Chemokine CXCL12; D009944:Organoplatinum Compounds; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042643:Vascular Endothelial Growth Factor D; D000077150:Oxaliplatin; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine