Ovarian Cancer Cells Modulate Human Blood Neutrophils Response to Activation In Vitro

Abstract

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.

The emerging role of CXC chemokines in epithelial ovarian cancer

“…Once present, neutrophils secrete a broad spectrum of proteases including cathepsin G that can cleave CXCL5; N-terminal truncation of CXCL5 significantly enhances the chemotactic potency of CXCL5 both in vitro and in vivo (Wuyts et al 1999, Mortier et al 2010. Neutrophils isolated from the peripheral blood of ovarian cancer patients also produce increased reactive oxygen species and display increased adhesion to ovarian cancer cells through enhanced CD11b/ CD18 expression on their cell surfaces (Klink et al 2008). The adhesion of neutrophils to endothelial cells initiates remodelling of the endothelium, making it easier for tumour cells to metastasise (Wu et al 2001, De Larco et al 2004, Klink et al 2008.…”

“…Neutrophils isolated from the peripheral blood of ovarian cancer patients also produce increased reactive oxygen species and display increased adhesion to ovarian cancer cells through enhanced CD11b/ CD18 expression on their cell surfaces (Klink et al 2008). The adhesion of neutrophils to endothelial cells initiates remodelling of the endothelium, making it easier for tumour cells to metastasise (Wu et al 2001, De Larco et al 2004, Klink et al 2008. Figure 4 attempts to summarise the influence of neutrophils and modified CXCL5 in the metastasis of ovarian tumour cells.…”

Role of LFA-1 and ICAM-1 in Cancer

“…Importantly, the neutrophil-cancer cell interactions mediated by LFA-1 facilitated breast cancer dissemination [18]. In ovarian cancer patients, the adhesive properties of blood neutrophils are increased, due to a higher expression of CD11b/CD18 integrin, suggesting that the neutrophil-cancer cell contacts modify the properties of neutrophils to facilitate tumor dissemination [20].…”

“…Importantly, the neutrophil-cancer cell interactions mediated by LFA-1 facilitated breast cancer dissemination [18]. In ovarian cancer patients, the adhesive properties of blood neutrophils are increased, due to a higher expression of CD11b/CD18 integrin, suggesting that the neutrophil-cancer cell contacts modify the properties of neutrophils to facilitate tumor dissemination [20].By contrast, in other types of cancer, neutrophils play a surveillance role against tumor development [21]. When this is the case, it would be desirable to potentiate neutrophil infiltration into the tumor to increase its elimination.…”

Caracterização da resposta imune celular em mulheres com câncer de ovário

“…Por outro lado, um estudo demonstrou que o aumento da expressão de CD18 em neutrófilos de mulheres com câncer de ovário estadios III e IV estava associado com o aumento do potencial metastático tumoral [49]. Não verificamos diferença estatística entre os grupos em relação à análise das moléculas de adesão celular (CD54, CD62L e CD18), exceto para a molécula CD62L que reduziu sua expressão entre o grupo de mulheres com neoplasia ovariana benigna quando comparado com o controle (P<0,039).…”