Recombinant human granulocyte colony‐stimulating factor inhibits the metastasis of hematogenous and non‐hematogenous tumors in mice

Abstract

We studied the effects of in vivo administrations of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the metastasis of murine hematogenous and non-hematogenous tumors in spontaneous and experimental metastasis models. Spontaneous lung metastasis caused by intra-footpad injections of B16-BL6 melanoma and Lewis-lung-carcinoma (3LL) cells were inhibited by intravenous (i.v.) and subcutaneous (s.c.) injections of rhG-CSF after excision of the primary tumors. Recombinant hG-CSF significantly inhibited liver metastasis when administered i.v. after i.v. injection of L5178Y-ML25 T-lymphoma cells. Multiple i.v. administration of rhG-CSF after the tumor inoculation prolonged the survival times of mice inoculated i.v. with L5178Y-ML25 lymphoma cells. Recombinant hG-CSF did not directly affect the growth of B16-BL6 and L5178Y-ML25 cells in vitro. During the administration periods, both i.v. and s.c. injections of rhG-CSF increased the number of total white blood cells (WBC) in peripheral blood to approximately 3 times the normal level in normal and tumor-bearing mice. We also found that the administration of rhG-CSF stimulates neutrophils to become cytostatic against these tumor cells. Our results indicate that the injection of rhG-CSF is effective in inhibiting lung and liver metastases by activating neutrophils and increasing cell number.

An Important Role for Granulocytes in the Thermal Regulation of Colon Tumor Growth

“…Interestingly, circulating granulocytes in many cancer patients have been reported to be impaired in their ability to produce superoxide anion (Hara et al, 1992), to perform antibody-dependent tumor cell lysis (Dallegri et al, 1989), and to mobilize in vivo to skin chambers (Frumento et al, 1984). While PMNs are normally a scarce reactive component of both human and animal tumors (Di Carlo et al, 2001), it has been suggested that these cells are active in immunosurveillance against several tumors (Di Carlo et al, 2001;Matsumoto et al, 1991;Midorikawa et al, 1990). During rIL-2 infusion in patients with malignant melanoma and renal cell carcinoma, there has been phenotypic and functional evidence of potent PMN activation (Di Carlo et al, 2001).…”

Kaposi's Sarcoma-Associated Herpesvirus Infection of Endothelial Cells Inhibits Neutrophil Recruitment through an Interleukin-6-Dependent Mechanism: a New Paradigm for Viral Immune Evasion

“…Interestingly, highly increased hIL-6 expression is a common feature of many tumor cells aside from those found in KS (5,38,72,78); thus, IL-6 and SOCS3 could act in a wider context in immunomodulation in tumor biology. Neutrophil exclusion from KS lesions is likely to have pathological implications, as several studies strongly support the concept that they are important in immunosurveillance against various tumor types (18,43,44). Neutrophils, which are recruited early to such sites, produce cytotoxic mediators, including proteases, reactive oxygen species, and soluble mediators of cell killing, and antiviral agents such as TNF-␣ and gamma interferon (IFN-␥) (34).…”

A novel glioblastoma cancer gene therapy using AAV-mediated long-term expression of human TERT C-terminal polypeptide

“…46 It has been reported that activated PMNs play a key role in immunosurveillance against several tumors, such as melanoma, lung carcinoma and adenocarcinoma. [47][48][49] In cooperation with CD8 þ cells, they are also involved in the cytokine-induced tumor rejections. 50 In this context, it is likely that the immune responses elicited by rAAV-hTERTC27 will be even more prominent in immunocompetent animals.…”