The acellular fraction of stored platelets promotes tumor cell invasion.
BACKGROUND
Transfusion of blood products is a potentially life-saving treatment to correct deficits of volume status or oxygen delivery. Increasingly it has been recognized that transfusions also transmit immunosuppressive factors including cytokines and lipid mediators. Platelets are ubiquitously present in blood transfusions and contain numerous growth factors that may contribute to tumor growth. We hypothesized that such growth factors released during routine platelet storage promote cancer invasion.


METHODS
Modified Boyden chamber transwell invasion assays were performed to determine if factors released into the plasma portion of stored platelets could induce tumor cell invasion.


RESULTS
Soluble mediators from stored platelets induce invasion in two pancreatic cancer cell lines (MIA PaCA-2, Pan02) and one breast cancer cell line (MDA-MB-231). Additionally, we show that vascular endothelial growth factor is present in the acellular fraction of stored platelets and that inhibition of vascular endothelial growth factor with bevacizumab reduces tumor cell invasion in vitro. Finally, we found that in vivo administration of this acellular fraction increases tumor angiogenesis.


CONCLUSIONS
Components in stored platelets can promote the invasion of multiple cancer cell lines in vitro. These results indicate that factors in platelets may mediate deleterious effects associated with transfusion in cancer patients.
Division of Surgical Oncology, Department of Surgery, University of Texas Southwestern Medical School, Dallas, Texas 75390, USA.
Sean P
SP
Dineen
Christina L
CL
Roland
Jason E
JE
Toombs
Marguerite
M
Kelher
Christopher C
CC
Silliman
Rolf A
RA
Brekken
Carlton C
CC
Barnett
D043925:Angiogenesis Inducing Agents / Q000276:immunology; D000818:Animals; D001792:Blood Platelets / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology; D051379:Mice; D009361:Neoplasm Invasiveness / Q000276:immunology; D009389:Neovascularization, Pathologic / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology; D017713:Platelet Transfusion / Q000009:adverse effects*; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology*
D043925:Angiogenesis Inducing Agents; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A