Up-regulation of pro-angiogenic factors and establishment of tolerance in malignant pleural effusions.
BACKGROUND
Malignant pleural effusions (MPEs) are a significant source of cancer morbidity and mortality. Currently there is no cure for MPEs and treatments only palliate the symptoms. The purpose of this study was to determine if there are differences in markers of angiogenesis and immune phenotypes between adenocarcinoma-induced MPEs and benign pleural effusions (BPEs).


METHODS
Pleural effusions were collected from patients with MPEs and BPEs. Cells were isolated from effusions and characterized using fluorescent cell sorting (FACS). Pleural effusions were evaluated by ELISA for VEGF-A. An angiogenesis protein array was completed to compare protein expression in malignant and non-malignant effusions.


RESULTS
FACS analysis demonstrated lower accumulation of cytotoxic T-cells and significantly higher accumulation of monocytes, dendritic cells, mesothelial and tumor cells in MPEs compared to benign pleural effusions. MPEs were found to have 77-fold higher VEGF-A levels compared to BPEs. The angiogenesis protein array demonstrated elevated levels of pro-angiogenic factors VEGF-A, CXCL4 and MMP-8, and low levels of pro-inflammatory cytokines IL-8, MCP-1, and TGF-β1 in MPEs.


CONCLUSIONS
MPE is biased toward a Th2 dominant state. There is an increase in expression of VEGF-A and other pro-angiogenic factors in MPE. These data suggest there is a role for anti-angiogenesis therapy in patients with MPEs.
Mayo Graduate School, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, United States.
Elizabeth Ann T
EA
Lieser
Gary A
GA
Croghan
Wendy K
WK
Nevala
Michael J
MJ
Bradshaw
Svetomir N
SN
Markovic
Aaron S
AS
Mansfield
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D010978:Platelet Factor 4 / Q000378:metabolism; D016066:Pleural Effusion, Malignant / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D014408:Biomarkers, Tumor; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D010978:Platelet Factor 4; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8
Angiogenesis; Benign pleural effusion; Chronic inflammation; Immunity; Malignant pleural effusion; Vascular endothelial growth factor (VEGF)