HA in pathological and physiological processes: An overview of HA metabolism in cancer and pregnancy

Abstract

Hyaluronan (HA) is a glycosaminoglycan component of the extracellular matrix, where it possesses functions in morphogenesis, tissue injury and repair, inflammation, and tumorigenesis. HA is synthesized by HA synthases (HAS) and is degraded by hyaluronidases (HYAL). Increased levels of HA in tumors, due to differential expression of HAS and HYAL, are related to tumor progression and metastasis. During pregnancy, changes in HA deposition and distribution indicate that HA participates in preparation of the endometrial stroma for reception of the embryo. While pregnancy is a physiological state and cancer a complex and unpredictable pathology, both trophoblast and tumor cells share some proliferative, invasive, and immune tolerance mechanisms that allow establishment of pregnancy and tumor progression. This indicates that the study of a physiological condition such as pregnancy could help to find novel cancer treatment strategies. Abnormal HA metabolism has been observed in cancer and pathologies of pregnancy, thus indicating that HA could be considered a key molecule, able to regulate these processes. This review discusses the role of HA in cancer and pregnancy: the study of similarities and differences between both models could lead to identification of new targets for treatment of tumors or pregnancy-associated pathologies.