Enhancement of in vitro prostaglandin E2 production by mouse fibrosarcoma cells after co-culture with various anti-tumour effector cells

Okada, Futoshi; Hosokawa, Masuo; Hasegawa, Junji; Kuramitsu, Yasuhiro; Nakai, Kazumoto; Liu, Yuan; Lao, Haiyan; Kobayashi, Hiroshi; Takeichi, Noritoshi

doi:10.1038/bjc.1994.285

Cited by 19 publications

(10 citation statements)

References 16 publications

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“…We have reported that inflammation-derived active oxygen species and cytokine/growth factors played major roles in the tumor progression Okada et al, 1992Okada et al, , 1994Okada et al, , 1999.…”

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confidence: 99%

Conversion of Human Colonic Adenoma Cells to Adenocarcinoma Cells Through Inflammation in Nude Mice

Okada

Kawaguchi

Habelhah

et al. 2000

Laboratory Investigation

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SUMMARY:The roles of inflammation in the malignant progression of tumors during multistep carcinogenesis have been much discussed but remain to be elucidated. To determine the direct contribution of inflammation to colon carcinogenesis, we established a new model of progression of human colonic adenoma cells using a nude mouse; the progression is accelerated by coimplantation of a plastic plate. The FPCK-1-1 cell line, derived from a colonic polyp in a patient with familial adenomatous polyposis, is nontumorigenic when injected subcutaneously into nude mice in a cell suspension of up to 5 ϫ 10 6 cells per mouse. However implantation of 1 ϫ 10 5 FPCK-1-1 cells attached to a plastic plate induced first acute and then chronic inflammation, and formed progressively growing tumors that were histologically determined as moderately differentiated adenocarcinoma in 65% of mice. Moreover cell lines established from the growing tumors were found to be tumorigenic when injected into mice even without a plastic plate. The tumor arising from the adenoma cells implanted attached to a plastic plate was surrounded by highly proliferating fibrous stroma. This fibrous tissue was considered essential for malignant progression, rather than for attachment to the plastic plate substrate, because the tumors were formed after injection of FPCK-1-1 cells into the fibrous tissue from which the plastic plate had been removed before the cell injection. The conditioned medium (CM) obtained from the fibroblasts derived from a plastic plate-associated stromal tissue was found to contain factors that stimulated growth of FPCK-1-1 cells, but not of the derivative progressor cell lines. The factor was stable to heating and neuraminidase treatment, but labile to trypsin treatment. The main growth-potentiating activity was contained in the fraction larger than 100 kDa. In contrast, the activity to promote FPCK-1-1 cell growth was not present in the CM of subcutaneous fibroblasts from untreated nude mice or the fibroblast cell lines C3H10T 1/2 and NIH3T3. These results demonstrated that inflammation-associated stroma promoted the conversion of colonic adenoma cells to adenocarcinoma cells. (Lab Invest 2000, 80:1617-1628.

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confidence: 99%

Conversion of Human Colonic Adenoma Cells to Adenocarcinoma Cells Through Inflammation in Nude Mice

Okada

Kawaguchi

Habelhah

et al. 2000

Laboratory Investigation

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“…Samlowski et al (2003) demonstrated that administration of SOD mimetic nonpeptidic molecule enhanced the cytotoxicity of lymphokine-activated killer (LAK) cells in vivo. Indeed, the QR-32 tumour cells are highly sensitive to LAK cells (Okada et al, 1994). Third is that oxykine might stimulate immune cells to produce SOD-inducible cytokines and growth factors.…”

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confidence: 99%

Prevention of inflammation-mediated acquisition of metastatic properties of benign mouse fibrosarcoma cells by administration of an orally available superoxide dismutase

Okada

Shionoya²,

Kobayashi

et al. 2006

Br J Cancer

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Weakly tumorigenic and nonmetastatic QR-32 cells derived from a fibrosarcoma in C57BL6 mouse are converted to malignant cells once they have grown after being coimplanted with a gelatine sponge which induces inflammation. We administered a newly developed peroral superoxide dismutase (SOD), oxykine, and as control vehicle, gliadin and saline, starting 2 days before the coimplantation and continued daily throughout the experiment. In the oxykine group, tumour incidence was lower (41%) than in the gliadin or saline group (83 and 79%, respectively). The inhibitory effect of oxykine was lost when an individual component of oxykine was administered, that is, SOD alone and gliadin alone. The effect was also abolished when administered by intraperitoneal route. When perfused in situ with nitroblue tetrazolium, an indicator of superoxide formation, the tumour masses from gliadin and saline groups displayed intense formazan deposition, whereas, those from oxykine group had less deposition. Enzymatic activity of SOD was also increased in oxykine group. Arising tumour cells in gliadin and saline groups acquired metastatic phenotype, but those in oxykine group showed reduced metastatic ability. These results suggested that the orally active SOD derivative prevented tumour progression promoted by inflammation, which is thought to be through scavenging inflammatory cell-derived superoxide anion.

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“…The endogenous source of cytokines/growth factors is known to be involved in the process of tumour progression (Films and Kerbel, 1993;Leek et al, 1994;Okada et al, 1994;Shimoda et al, 1994;Nagayasu et al, 1998). Moreover, recent data indicate that such cytokines/growth factors cause reduction of antioxidative enzyme expressions in normal cells, and set out a speculation that suppression of antioxidative enzymes may lead to greater susceptibility to the oxidative damage and to carcinogenesis (Kayanoki et al, 1994;Suemizu et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…Our previous studies revealed that the co-implantation of the gelatin sponge with tumour cells induced inflammation at the site of tumour growth, and that the reactive inflammatory cells participated in the progression of QR-32 cells (Okada et al, 1992). We speculated that various active oxygen species produced by such inflammatory cells contributed to the tumour-promoting process with their mutagenic effects on tumour cells (Okada et al, 1992(Okada et al, , 1994. In fact, tumour cell lines established from the tumours arising in mice with QR cells co-implanted with foreign bodies such as gelatin sponge or plastic plate acquired stable malignant phenotypes (Young et al, 1991;Okada et al, 1992Okada et al, , 1993.…”

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confidence: 99%

Inflammatory cell-mediated tumour progression and minisatellite mutation correlate with the decrease of antioxidative enzymes in murine fibrosarcoma cells

et al. 1999

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We isolated six clones of weakly tumorigenic fibrosarcoma (QR) from the tumorigenic clone BMT-11 cl-9. The QR clones were unable to grow in normal C57BL/6 mice when injected s.c. (1 × 10 5 cells). However, they formed aggressive tumours upon co-implantation with a ‘foreign body’, i.e. a gelatin sponge, and the rate of tumour take ranged from 8% to 58% among QR clones. The enhanced tumorigenicity was due to host cell-mediated reaction to the gelatin sponge (inflammation). Immunoblot analysis and enzyme activity assay revealed a significant inverse correlation between the frequencies of tumour formation by QR clones and the levels of manganese superoxide dismutase (Mn-SOD, P <0.005) and glutathione peroxidase (GPχ, P <0.01) in the respective tumour clones. Electron spin resonance (ESR) revealed that superoxide-scavenging ability of cell lysates of the QR clone with high level of Mn-SOD was significantly higher than that with low level of the antioxidative enzyme in the presence of potassium cyanide, an inhibitor for copper–zinc superoxide dismutase (CuZn-SOD) ( P <0.001). Minisatellite mutation (MSM) induced by the inflammatory cells in tumour cells were investigated by DNA fingerprint analysis after QR clones had been co-cultured with gelatin-sponge-reactive cells. The MSM rate was significantly higher in the subclones with low levels of Mn-SOD and GPχ ( P <0.05) than in the subclones with high levels of both enzymes. The MSM of the subclones with low levels of both enzymes was inhibited in the presence of mannitol, a hydroxyl radical scavenger. The content of 8-hydroxydeoxyguanosine (8-OHdG) by which the cellular DNA damage caused by active oxygen species can be assessed was significantly low in the tumours arising from the QR clone with high levels of Mn-SOD and GPχ even if the clone had been co-implanted with gelatin sponge, compared with the arising tumour from the QR clone with low levels of those antioxidative enzymes ( P <0.001). In contrast, CuZn-SOD and catalase levels in the six QR clones did not have any correlation with tumour progression parameters. These results suggest that tumour progression is accelerated by inflammation-induced active oxygen species particularly accompanied with declined levels of intracellular antioxidative enzymes in tumour cells. © 1999 Cancer Research Campaign

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Enhancement of in vitro prostaglandin E2 production by mouse fibrosarcoma cells after co-culture with various anti-tumour effector cells

Abstract: SaryWe have previously reported that an increase in the production of immunosuppressive prostaglandin E2 by a QR tumour

Cited by 19 publications

References 16 publications

Conversion of Human Colonic Adenoma Cells to Adenocarcinoma Cells Through Inflammation in Nude Mice

Conversion of Human Colonic Adenoma Cells to Adenocarcinoma Cells Through Inflammation in Nude Mice

Prevention of inflammation-mediated acquisition of metastatic properties of benign mouse fibrosarcoma cells by administration of an orally available superoxide dismutase

Inflammatory cell-mediated tumour progression and minisatellite mutation correlate with the decrease of antioxidative enzymes in murine fibrosarcoma cells

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