Prostaglandin E2 Promotes Tumor Progression by Inducing Myeloid-Derived Suppressor Cells

摘要: A causative relationship between chronic inflammation and cancer has been postulated for many years, clinical observations laboratory experiments support the hypothesis that contributes to tumor onset progression. However, precise mechanisms underlying are not known. We recently reported proinflammatory cytokine, interleukin-1beta, induces accumulation retention of myeloid-derived suppressor cells (MDSC), which commonly found in patients experimental animals with potent suppressors adaptive innate immunity. This finding led us hypothesize leads through induction MDSC, inhibit immunosurveillance thereby allow unchecked persistence proliferation premalignant malignant cells. now report host MDSC have receptors prostaglandin E2 (PGE2) E-prostanoid receptor agonists, including PGE2, induce differentiation Gr1(+)CD11b(+) from bone marrow stem cells, whereas antagonists block differentiation. BALB/c EP2 knockout mice inoculated spontaneously metastatic BALB/c-derived 4T1 mammary carcinoma delayed growth reduced numbers relative wild-type mice, suggesting PGE2 partially mediates receptor. Treatment 4T1-tumor-bearing cyclooxygenase 2 inhibitor, SC58236, delays primary reduces accumulation, further showing providing a therapeutic approach reducing this tumor-promoting cell population.