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The role of Prostaglandin D2 in cancer associated inflammation

Cancer associated inflammation is well known to contribute to tumour progression,and pro-inflammatory mediators, including cytokines and prostaglandins, can drive malignancy. Prostaglandins are generated from arachidonic acid by t... ver más

31/08/2011

INSERM

165K€

Presupuesto del proyecto: 165K€

Líder del proyecto

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHER... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2011-08-31 No tenemos la información de la convocatoria

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Líder del proyecto

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHER... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 165K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Cancer associated inflammation is well known to contribute to tumour progression,and pro-inflammatory mediators, including cytokines and prostaglandins, can drive malignancy. Prostaglandins are generated from arachidonic acid by the action of cyclooxygenase (COX), and include PGE2 as a major pro-inflammatory mediator, and PGD2 that has anti-inflammatory activity. While it is well known that PGE2 promotes tumourogenesis, there is little known about the role of PGD2 in cancer. Our aim is to establish the role of PGD2 in tumour progression in vivo using a syngeneic transplantable mouse model of ovarian cancer and a two-stage skin carcinogenesis model. We also aim to investigate the role of PGD2 in modulation of cancer-associated inflammation and tumour-associated macrophage (TAM) phenotype. We will use a mouse ovarian cancer model that recapitulates the peritoneal spread of stage IV human ovarian cancer. We will evaluate the role of PGD2 and its’ receptor, DP-1, using transgenic mice and synthetic agonists/antagonists. We will also use a two-stage skin carcinogenesis model to study the role of PGD2 in carcinogen-induced inflammation-associated cancer. There is a great deal on interest in the therapeutic use of COX inhibitors in cancer, we hypothesise that the potential benefits of COX inhibitors in inflammation-associated cancer may be hampered by inhibition of protective, anti-inflammatory PGD2. Our preliminary data suggest PGD2 is indeed protective in a mouse model of stage IV ovarian cancer. These further studies will not only establish a rationale for selective inhibition of prostaglandin synthesis rather than COX in ovarian cancer but may also suggest DP-1 receptor agonists could offer a new therapeutic avenue in inflammation-associated cancer.

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