Hyal2 Expression in Tumor-Associated Myeloid Cells Mediates Cancer-Related Inflammation in Bladder Cancer

Abstract The increased presence of myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) in tumor tissue has been extensively reported. However, their role the regulation hyaluronan (HA) metabolism microenvironment not established. Here we describe a novel function myeloid related to enhanced breakdown extracellular HA human bladder cancer tissue, leading accumulation small fragments with molecular weight (MW) <20 kDa. Increased fragmentation low (LMW-HA) was associated elevated production multiple inflammatory cytokines, chemokines, angiogenic factors. by mediated membrane-bound enzyme hyaluronidase 2 (Hyal2). numbers Hyal2+CD11b+ were detected as well peripheral blood patients cancer. Coexpression CD33 suggested that these belong monocytic cells. HA-degrading Hyal2-expressing MDSCs could be exposure tumor-conditioned medium, IL1β identified one factors involved stimulation Hyal2 activity. CD44-mediated signaling played an important activity cells, engagement CD44 receptor specific mAb triggered translocation cellular surface stimulated secretion IL1β. Taken together, this work identifies key players LMW-HA cancer-related inflammation angiogenesis. Significance: This study monocyte–macrophage lineage contributors degradation proangiogenic fragments.