Physically modified hyaluronan in cancer prevention

Abstract

Although oligomeric HA may exhibit cancer‐blocking function, the functional role of hyaluronan (HA) in blocking or promoting cancer growth is largely controversial. When immune deficient or competent mice were pre‐injected with high molecular weight or native HA (medical grade), these mice became highly susceptible to the growth of melanoma and many cancer xenografts. However, when native HA was subjected to partial degradation and conformational alteration by appropriate physical approaches (e.g. UV irradiation, heat treatment, etc), one of the HA preparations, designated HAson, provided a long‐term prevention of the growth of skin cancer, melanoma, breast adenocarcinoma, and many other cancers in mice. A specific hyaluronidase Hyal‐2 antibody reproduced the induced cancer prevention. Further, HAson‐induced anticancer activity is memorized in the non‐T/non‐B Hyal‐2+ spleen cells, as the induced anticancer activity can be transferred to naïve immune‐deficient mice via spleen cells. Together, HAson binds and activates memory Hyal‐2+ spleen cells via the Hyal‐2/WWOX/Smad4 signaling to potently elicit long‐term cancer prevention in vivo. (Supported in part by NHRI and DOD, Taiwan, and DoD, USA)