Ovarian cancer cells modulate human blood neutrophils response to activation in vitro.
In cancer, numerous cells of both innate and adaptive immune systems are activated. Polymorphonuclear neutrophils are potent effector cells of inflammation that are an important component of tumour development and progression. The important signalling proteins that are involved in neutrophil functions are extracellular signal-regulated kinases 1/2 (ERK1/2). We investigated the reactive oxygen species (ROS) production, adhesive ability and CD11b/CD18 adhesion molecule expression on neutrophils isolated from peripheral blood of ovarian cancer patients and the in vitro response of these cells to stimuli and direct contact with ovarian cancer cells isolated from tumour. We found that functional activities of neutrophils isolated from patients with advanced stages of ovarian cancer (FIGO III/IV) were intensified in comparison to neutrophils isolated from healthy female volunteers. Neutrophils of cancer patients produce higher amounts of ROS in response to stimuli than those of control group. Unstimulated neutrophils of patients possess higher expression of CD11b/CD18 molecule that is accompanied by increased adhesive ability of these cells. Our results reveal that augmented functional activities of neutrophils may result from the intensification of ERK1/2 kinases phosphorylation. We found that interactions with ovarian cancer cells modulate neutrophil functions as a result of cell-to-cell direct contact. We conclude that ovarian cancer cells affect pro-inflammatory activities in neutrophils via influence of signalling pathways in response to stimuli. Our results suggest the possibility that neutrophils responding to contact with cancer cells contribute to the progression and metastatic potential of tumour cells.
Klink
M
M
Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland. mklink@cbm.pan.pl
Jastrzembska
K
K
Nowak
M
M
Bednarska
K
K
Szpakowski
M
M
Szyllo
K
K
Sulowska
Z
Z
D000328:Adult; D000368:Aged; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D008875:Middle Aged; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009367:Neoplasm Staging; D018375:Neutrophil Activation; D009504:Neutrophils / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology; D010053:Ovary / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D039481:CD11b Antigen; D018821:CD18 Antigens; D017382:Reactive Oxygen Species; D048052:Mitogen-Activated Protein Kinase 3