Hyaluronan Receptors as Mediators and Modulators of the Tumor Microenvironment

Abstract The tumor microenvironment (TME) is a dynamic and complex matter shaped by heterogenous cancer and cancer‐associated cells present at the tumor site. Hyaluronan (HA) is a major TME component that plays pro‐tumorigenic and carcinogenic functions. These functions are mediated by different hyaladherins expressed by cancer and tumor‐associated cells triggering downstream signaling pathways that determine cell fate and contribute to TME progression toward a carcinogenic state. Here, the interaction of HA is reviewed with several cell‐surface hyaladherins—CD44, RHAMM, TLR2 and 4, LYVE‐1, HARE, and layilin. The signaling pathways activated by these interactions and the respective response of different cell populations within the TME, and the modulation of the TME, are discussed. Potential cancer therapies via targeting these interactions are also briefly discussed.