Oxidative burst and anticancer activities of rat neutrophils

Abstract

It is assumed that oxidative damage caused by reactive oxygen species (ROS) from activated neutrophil granulocytes may contribute to pathology of tumors. ROS are crucial in neutrophil-mediated tumor cell lysis. The present study is focused on the oxidative burst and antitumorous activities of neutrophils when challenged with Walker carcinoma W256. Survival and tumor growth dynamics were monitored in vivo, while tumor cell proliferation when mixed with neutrophils was studied in vitro together with the generation/release of neutrophil respiratory burst products, primarily 1O2. Neutrophils were collected upon Sephadex injection. The survival of Sephadex injected animals was slightly improved, while their tumors grew less than in controls. The presence of tumor cells in vitro activated neutrophils to produce singlet oxygen similar to phorbol ester. Neutrophils from Sephadex-bearing animals diminished tumor cell proliferation in vitro (measured by 3H-TdR incorporation), while neutrophils from Sephadex and the tumor-bearing animals did not show such activity in vitro. Our results confirm that in the case of rapidly growing tumors such as murine W256 carcinoma neutrophils have antitumorous effects in the early phase of tumor development.

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

“…Still, several antibacterial molecules are also involved in neutrophil cytotoxicity toward tumor cells. Of special importance are the reactive oxygen species H 2 O 2 and HOCl, generated during an "oxidative burst" that is mediated by the NADPH oxidase complex and by myeloperoxidase, respectively [325][326][327]. These molecules are directly involved in the anti-tumor activity [325][326][327].…”

“…Of special importance are the reactive oxygen species H 2 O 2 and HOCl, generated during an "oxidative burst" that is mediated by the NADPH oxidase complex and by myeloperoxidase, respectively [325][326][327]. These molecules are directly involved in the anti-tumor activity [325][326][327]. Inhibition of myeloperoxidase by azide or cyanide, or addition of catalase that catalyzes the conversion of hydrogen peroxide to water and oxygen, prevents neutrophilmediated tumor cell killing [13,32,309,[314][315][316][317][318].…”

Peritumoral administration of granulocyte colony-stimulating factor induces an apoptotic response on a murine mammary adenocarcinoma

“…21 However, several reports have emphasized the role of neutrophils as mediators of antitumor effects. [9][10][11][12]22 In particular, it has been reported that the transfer of G-CSF gene to colon adenocarcinoma C-26 cells inhibited tumor development, suggesting that the local release of G-CSF induces an antitumor response by recruitment of neutrophils and other mononuclear…”

Granulocytes as effective anticancer agent in experimental solid tumor models

“…It was demonstrated that the activated granulocytes cause unspecific lysis of tumor cells mediated by ROS (Dallegri et al, 1991;van Kessel et al, 1990;Lichtenstein et al, 1989), hence ROS have been identified as effector molecules of the oxygendependent killing of cancer cells by granulocytes (Lichtenstein and Kahle, 1985;Lichtenstein et al, 1989). We have found that oxidative burst of granulocytes is cytotoxic for melanoma B16-F10 (Zivkovic et al, 2007) and for Walker 256 carcinoma (W256) (Zivkovic et al, 2005a). However, in spite of the data showing that granulocytes can participate in destruction of malignant cells, little is known about function of granulocytes in tumor-bearing hosts.…”

“…In a previous study (Zivkovic et al, 2005a), we have found that functional granulocytes, obtained from the papula of normal, healthy rats injected subcutaneously (s.c.) with Sephadex, act cytotoxically against W256 tumor cells in vitro. Moreover, the granulocytes from the Sephadex papula of the tumor-bearing animals were less reactive in vitro than the granulocytes from the Sephadex papula of the normal healthy animals, indicating that the most potent granulocytes were already engaged in reaction against the W256 in vivo.…”