Role of Rip2 in Development of Tumor-Infiltrating MDSCs and Bladder Cancer Metastasis

• DOI: 10.1371/journal.pone.0094793
• Publication Date: 2014-04-14T20:40:42Z
• Authors: Hanwei Zhang; Arnold I. Chin
• Keywords: Tumor progression; Tumor-associated macrophage

Tumor invasion and metastases represent a complex series of molecular events that portends poor prognosis. The contribution inflammatory pathways mediating this process is not well understood. Nod-like receptors (NLRs) innate immunity function as intracellular sensors pathogen motifs danger molecules. We propose role NLRs in tumor surveillance programming tumor-infiltrating lymphocytes (TILs). In study, we examined the downstream serine/threonine tyrosine kinase Rip2 murine model bladder cancer. Rip2-deficient C57Bl6 mice, larger orthotopic MB49 tumors developed with more numerous higher incidence compared to wild-type controls. As such, increased infiltration CD11b+Gr1hi myeloid-derived suppressor cells (MDSCs) concomitant decrease T NK were observed bearing animals using subcutaneous models. showed enhanced epithelial-to-mesenchymal transition, elevated expression zeb1, zeb2, twist, snail microenvironment. found absence plays an intrinsic fostering development granulocytic MDSCs by autocrine paracrine effect colony stimulating factor (G-CSF) expression. Our findings suggest NLR may be novel modality program TILs influence metastases.