Chemokine gene transfection into tumour cells reduced tumorigenicity in nude mice in association with neutrophilic infiltration

Abstract

:awa LUniveritY. 13-1, Takara-machi, Kana:awa 920. Japan.Summarv To studv the effect of localised secretion of chemokines on tumour growth. the genes for human (hu interleukin 8 (IL-8). hu-MCP-1 (NICAF). hu-MIP-12 (LD78). murine (mu)-MCP-1 (JE). mu-MIP-lx or mu-MIP-2 A-ere introduced. v-ia mammalian expression vectors. into Chinese hamster ovarv (CHO) cells. and the abilitv of transfected cells to form tumours in vivo uas evaluated. The production of hu-IL-8. hu-MIP-lx or mu-MIP-lx bv transfected clones did not influence the growth rate in iitro. but drastically suppressed tumour growth A-hen injected subcutaneouslv (s.c.) into nude mice. However. clones transfected with hu-MCP-1. mu-NMCP-I or mu-MIP-2 did not shou-anv significant difference in growth rate in vivo compared u-ith clones transfected u-ith sector alone. Histological examination of the site of injection of CHO clones transfected w-ith hu-IL-8. hu-MIP-l1 or mu-MIP-lE showed predominantly neutrophilic infiltration. These results indicate that chemokines have potent anti-tumour activitv A-hen released. even at lou-doses. at the tumour site. A-hich mav be mediated by recruitment and targeting of neutrophilic granulocvtes to chemokinereleasing cells. Our studies highlight the potential usefulness of localised chemokine secretion in inducing potent host anti-tumour defensive responses.

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

“…42 IL-6 is frequently produced in glioblastoma cells, 43 whereas IL-8 is a chemokine, which promotes the directional migration of neutrophils, basophils and T-lymphocytes into the tumor growth area. 44,45 We speculate that upregulation of these immune response genes may enhance the general immunity of the treated mice to tumor cells by increasing the release of cytokines and infiltration of immune effector cells into the tumor growth areas. It is worth noting that the PMN infiltrates may account for the tumoricidal effects induced by rAAV-hTERTC27 treatment.…”

Interleukin‐8 modulates growth and invasiveness of estrogen receptor‐negative breast cancer cells

“…16,[18][19][20] Since IL-8 is a critical regulator of neutrophil activation and migration, 21 we postulate that the biological effects of IL-8 in vivo may be associated with its ability to regulate neutrophil infiltration. To test this hypothesis, we used immunocytochemistry to detect neutrophil on frozen tumor tissues.…”

“…Tumor volume (mm 3 ) was calculated using the formula: tumor size 5 ab 2 /2, where 'aÕ is the larger and 'bÕ is the smaller of the 2 dimensions. 16 To determine the stability of the IL-8 interference in vivo, blood was collected from the tails of nude mice bearing tumors at 2, 4 and 6 weeks after injection. The blood was centrifuged at 2,000 rpm for 10 min, and serum was collected and stored at 280°C until further testing by ELISA assay as described earlier.…”

Combined therapy of multidrug-resistant human lung cancer with anti-P-glycoprotein antibody and monocyte chemoattractant protein-1 gene transduction: The possibility of immunological overcoming of multidrug resistance

“…Some workers have reported the effect of transduction of the MCP-1 gene into fibroblasts and cancer cells (Rollins and Sunday, 1991;Bottazzi et al, 1992;Hirose et al, 1995). Rollins and Sunday (1991) showed a suppressive effect of JE gene-transfection on the tumorigenicity of CHO cells, but Bottazzi et al (1992) found that melanoma cells producing MCP-1 were more tumorigenic than control cells.…”