Role of VEGF-stromal cell-derived factor-1alpha/CXCL12 axis in pleural effusion of lung cancer.
OBJECTIVE
It has been suggested that stromal cell-derived factor-1alpha ((SDF-1alpha) or CXCL12, both transcripts, TR1 and TR2) and its cognate receptor CXCR4 may regulate cancer metastasis. We have investigated the role of vascular endothelial growth factor (VEGF), angiopoietins (Ang-1 and Ang-2) and the biological axis of CXCL12-CXCR4, in patients with malignant pleural effusions (PEs).


METHODS
Twenty five patients, seven with transudative PEs due to heart failure and 18 with exudative malignant PEs (7 with small cell lung cancer (SCLC) and 11 with nonsmall cell lung cancer (NSCLC)) were included in the study. Expression analysis of the mediators was performed in pleural fluid pellet using real-time reverse transcription-PCR. Protein expression has been evaluated by western blot analysis.


RESULTS
SDF-TR1 (P = 0.02) but not SDF-TR2 (P = 0.23) or CXCR4 levels (P = 0.23) were higher in malignant PEs than in transudates. SDF-TR1 (P = 0.04) and SDF- TR2 levels (P = 0.04) but not CXCR4 levels (P = 0.123) were higher in SCLC PEs than in heart failure PEs. SDF-TR1 (P = 0.03) but not SDF-TR2 levels (P = 0.6) and CXCR4 levels (P = 0.4) were higher in NSCLC PEs than in transudates. Ang-1 has not been expressed in PEs, whereas no significant difference has been detected in VEGF and Ang-2 expression between malignant PEs and transudates. However, protein expression showed increased VEGF and SDF expression in malignant PEs.


CONCLUSIONS
These results suggest that elevated SDF-1alpha/CXCL12 levels would be suggestive of a link to metastasis and may participate in pleural trafficking in lung cancer.
Economidou
Foteini
F
Department of Thoracic Medicine, Medical School, University of Crete, Greece.
Antoniou
Katerina M
KM
Soufla
Giannoula
G
Lasithiotaki
Ismini
I
Karagiannis
Konstantinos
K
Lymbouridou
Rena
R
Proklou
Athanasia
A
Spandidos
Demetrios A
DA
Siafakas
Nikolaos M
NM
D000368:Aged; D000369:Aged, 80 and over; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010996:Pleural Effusion / Q000378:metabolism*; D055752:Small Cell Lung Carcinoma / Q000201:enzymology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D042461:Vascular Endothelial Growth Factor A