TY - JOUR
T1 - Up-regulation of pro-angiogenic factors and establishment of tolerance in malignant pleural effusions
AU - Lieser, Elizabeth Ann T.
AU - Croghan, Gary A.
AU - Nevala, Wendy K.
AU - Bradshaw, Michael J.
AU - Markovic, Svetomir N.
AU - Mansfield, Aaron S.
N1 - Funding Information:
This study was supported by The Dr. Lynn Tschudy Memorial Fund and by an Eagle's Award #292 (Mayo Clinic). Authors would also like to thank Paul Scardino (Western Vision Software) for his help in developing the pixel density analysis software used for this study and Michael Thompson for his help in the processing and storage of samples.
PY - 2013/10
Y1 - 2013/10
N2 - Introduction: 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.
AB - Introduction: 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.
KW - Angiogenesis
KW - Benign pleural effusion
KW - Chronic inflammation
KW - Immunity
KW - Malignant pleural effusion
KW - Vascular endothelial growth factor (VEGF)
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U2 - 10.1016/j.lungcan.2013.07.007
DO - 10.1016/j.lungcan.2013.07.007
M3 - Article
C2 - 23948549
AN - SCOPUS:84884415390
SN - 0169-5002
VL - 82
SP - 63
EP - 68
JO - Lung Cancer
JF - Lung Cancer
IS - 1
ER -